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Gioacchini G, Filippi S, Cardillo C, De Simone K, Zarantoniello M, Mascoli A, Carnevali O, Colella S, Chemello G. Exploring Photoreceptor Gene Expression and Seasonal Physiology in Mediterranean Swordfish ( Xiphias gladius). Animals (Basel) 2024; 14:3273. [PMID: 39595325 PMCID: PMC11590907 DOI: 10.3390/ani14223273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Revised: 11/11/2024] [Accepted: 11/11/2024] [Indexed: 11/28/2024] Open
Abstract
Mature and immature female swordfish show different gonadal expression patterns of melatonin synthesis-related and opsin genes, indicating that seasonality affects gonadal circadian genes, especially through opsin modulation. The high energy demands of reproduction may cause mature female swordfish to become more susceptible to environmental stressors/changes, potentially affecting their health post-reproduction. The modulation of melatonin and opsin expression may also influence swordfish biology, impacting basal metabolism and stress responses. This study aimed to investigate the hepatic expression patterns of genes involved in melatonin and opsins activity after the reproductive period, comparing mature and immature females. Liver samples of swordfish females, collected from the Central Adriatic Sea, were analyzed to evaluate the expression of a melatonin receptor (mel1b), acetylserotonin O-methyltransferase (asmt), opsins (sws, VA opsin and opsin4), and stress response (sod1, sod2 and hsp4b) genes, while histological analysis focused on hepatic melanomacrophages, melanomacrophage centers, and lipid content. The expression of all genes analyzed did not differ between mature and immature females except for sws, which was significantly downregulated in mature females. The overall health conditions of mature and immature females appeared comparable, as suggested by the histological analysis and the absence of significant differences in the expression of stress response genes. Although the study used a limited number of samples and lacked a comparison between the reproductive and non-reproductive periods, the preliminary results suggest that opsins may play a role in modulating physiological processes beyond reproduction.
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Affiliation(s)
- Giorgia Gioacchini
- Dipartimento di Scienze della Vita e dell’Ambiente (DiSVA), Università Politecnica delle Marche, Via Brecce Bianche, 60131 Ancona, Itlay; (G.G.); (S.F.); (C.C.); (K.D.S.); (M.Z.); (A.M.); (O.C.)
- Consorzio Interuniversitario I.N.B.B., Via dei Carpegna 19, 00165 Rome, Italy
| | - Sara Filippi
- Dipartimento di Scienze della Vita e dell’Ambiente (DiSVA), Università Politecnica delle Marche, Via Brecce Bianche, 60131 Ancona, Itlay; (G.G.); (S.F.); (C.C.); (K.D.S.); (M.Z.); (A.M.); (O.C.)
| | - Chiara Cardillo
- Dipartimento di Scienze della Vita e dell’Ambiente (DiSVA), Università Politecnica delle Marche, Via Brecce Bianche, 60131 Ancona, Itlay; (G.G.); (S.F.); (C.C.); (K.D.S.); (M.Z.); (A.M.); (O.C.)
| | - Kevin De Simone
- Dipartimento di Scienze della Vita e dell’Ambiente (DiSVA), Università Politecnica delle Marche, Via Brecce Bianche, 60131 Ancona, Itlay; (G.G.); (S.F.); (C.C.); (K.D.S.); (M.Z.); (A.M.); (O.C.)
| | - Matteo Zarantoniello
- Dipartimento di Scienze della Vita e dell’Ambiente (DiSVA), Università Politecnica delle Marche, Via Brecce Bianche, 60131 Ancona, Itlay; (G.G.); (S.F.); (C.C.); (K.D.S.); (M.Z.); (A.M.); (O.C.)
| | - Alessia Mascoli
- Dipartimento di Scienze della Vita e dell’Ambiente (DiSVA), Università Politecnica delle Marche, Via Brecce Bianche, 60131 Ancona, Itlay; (G.G.); (S.F.); (C.C.); (K.D.S.); (M.Z.); (A.M.); (O.C.)
| | - Oliana Carnevali
- Dipartimento di Scienze della Vita e dell’Ambiente (DiSVA), Università Politecnica delle Marche, Via Brecce Bianche, 60131 Ancona, Itlay; (G.G.); (S.F.); (C.C.); (K.D.S.); (M.Z.); (A.M.); (O.C.)
- Consorzio Interuniversitario I.N.B.B., Via dei Carpegna 19, 00165 Rome, Italy
| | - Sabrina Colella
- National Research Council (CNR), Institute for Marine Biological Resources and Biotechnology (IRBIM), Largo Fiera della Pesca 2, 60125 Ancona, Italy
| | - Giulia Chemello
- Dipartimento di Scienze della Vita e dell’Ambiente (DiSVA), Università Politecnica delle Marche, Via Brecce Bianche, 60131 Ancona, Itlay; (G.G.); (S.F.); (C.C.); (K.D.S.); (M.Z.); (A.M.); (O.C.)
- Consorzio Interuniversitario I.N.B.B., Via dei Carpegna 19, 00165 Rome, Italy
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Nadri P, Zahmatkesh A, Bakhtari A. The potential effect of melatonin on in vitro oocyte maturation and embryo development in animals. Biol Reprod 2024; 111:529-542. [PMID: 38753882 DOI: 10.1093/biolre/ioae077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2024] [Revised: 05/11/2024] [Accepted: 05/13/2024] [Indexed: 05/18/2024] Open
Abstract
Melatonin is a hormone mainly secreted by the pineal gland during the circadian cycle, with low levels during the daytime and prominent levels during the night. It is involved in numerous physiological functions including the immune system, circadian rhythm, reproduction, fertilization, and embryo development. In addition, melatonin exerts anti-inflammatory and antioxidant effects inside the body by scavenging reactive oxygen and reactive nitrogen species, increasing antioxidant defenses, and blocking the transcription factors of pro-inflammatory cytokines. Its protective activity has been reported to be effective in various reproductive biotechnological processes, including in vitro maturation (IVM), embryo development, and survival rates. In this comprehensive review, our objective is to summarize and debate the potential mechanism and impact of melatonin on oocyte maturation and embryo development through various developmental routes in different mammalian species.
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Affiliation(s)
- Parisa Nadri
- Department of Animal Science, College of Agriculture, Isfahan University of Technology, Isfahan, Iran
| | - Azadeh Zahmatkesh
- Department of Anaerobic Bacterial Vaccines Research and Production, Razi Vaccine and Serum Research Institute (RVSRI), Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran
| | - Azizollah Bakhtari
- Department of Animal Science, University of Connecticut, Storrs, CT, USA
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Li G, Yan L, Wang L, Ma W, Wu H, Guan S, Yao Y, Deng S, Yang H, Zhang J, Zhang X, Wu H, He C, Ji P, Lian Z, Wu Y, Zhang L, Liu G. Ovarian overexpression of ASMT gene increases follicle numbers in transgenic sheep: Association with lipid metabolism. Int J Biol Macromol 2024; 269:131803. [PMID: 38670205 DOI: 10.1016/j.ijbiomac.2024.131803] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2023] [Revised: 03/21/2024] [Accepted: 03/30/2024] [Indexed: 04/28/2024]
Abstract
Melatonin plays an important role in mammalian reproductive activities, to further understand the effects of endogenous melatonin on functions of ovary, the transgenic sheep with overexpression of melatonin synthetic enzyme gene ASMT in ovary were generated. The results showed that total melatonin content in follicular fluid of transgenic sheep was significantly greater than that in the wild type. Accordingly, the follicle numbers of transgenic sheep were also significantly greater than those in the WT. The results of follicular fluid metabolites sequencing showed that compared with WT, the differential metabolites of the transgenic sheep were significantly enriched in several signaling pathways, the largest number of metabolites was lipid metabolism pathway and the main differential metabolites were lipids and lipoid molecules. SMART-seq2 were used to analyze the oocytes and granulosa cells of transgenic sheep and WT sheep. The main differential enrichment pathway was metabolic pathway, in which lipid metabolism genes accounted for the majority. In conclusion, this is the first report to show that ovary overexpression of ASMT increased local melatonin production and follicle numbers. These results may imply that ASMT plays an important role in follicle development and formation, and melatonin intervention may be a potential method to promote this process.
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Affiliation(s)
- Guangdong Li
- National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, Beijing Key Laboratory of Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - Laiqing Yan
- National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, Beijing Key Laboratory of Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - Likai Wang
- National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, Beijing Key Laboratory of Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - Wenkui Ma
- National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, Beijing Key Laboratory of Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - Hao Wu
- National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, Beijing Key Laboratory of Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - Shengyu Guan
- National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, Beijing Key Laboratory of Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - Yujun Yao
- National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, Beijing Key Laboratory of Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - Shoulong Deng
- Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing 100021, China
| | - Hai Yang
- National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, Beijing Key Laboratory of Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - Jinlong Zhang
- Institute of Animal Husbandry and Veterinary, Academy of Agricultural Sciences of Tianjin, Tianjin 300112, China
| | - Xiaosheng Zhang
- Institute of Animal Husbandry and Veterinary, Academy of Agricultural Sciences of Tianjin, Tianjin 300112, China
| | - Haixin Wu
- National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, Beijing Key Laboratory of Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - Changjiu He
- College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China
| | - Pengyun Ji
- National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, Beijing Key Laboratory of Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - Zhengxing Lian
- National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, Beijing Key Laboratory of Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - Yingjie Wu
- National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, Beijing Key Laboratory of Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - Lu Zhang
- National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, Beijing Key Laboratory of Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - Guoshi Liu
- National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, Beijing Key Laboratory of Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.
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Horodincu L, Solcan C. Influence of Different Light Spectra on Melatonin Synthesis by the Pineal Gland and Influence on the Immune System in Chickens. Animals (Basel) 2023; 13:2095. [PMID: 37443893 DOI: 10.3390/ani13132095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 06/12/2023] [Accepted: 06/21/2023] [Indexed: 07/15/2023] Open
Abstract
It is well known that the pineal gland in birds influences behavioural and physiological functions, including those of the immune system. The purpose of this research is to examine the endocrine-immune correlations between melatonin and immune system activity. Through a description of the immune-pineal axis, we formulated the objective to determine and describe: the development of the pineal gland; how light influences secretory activity; and how melatonin influences the activity of primary and secondary lymphoid organs. The pineal gland has the ability to turn light information into an endocrine signal suitable for the immune system via the membrane receptors Mel1a, Mel1b, and Mel1c, as well as the nuclear receptors RORα, RORβ, and RORγ. We can state the following findings: green monochromatic light (560 nm) increased serum melatonin levels and promoted a stronger humoral and cellular immune response by proliferating B and T lymphocytes; the combination of green and blue monochromatic light (560-480 nm) ameliorated the inflammatory response and protected lymphoid organs from oxidative stress; and red monochromatic light (660 nm) maintained the inflammatory response and promoted the growth of pathogenic bacteria. Melatonin can be considered a potent antioxidant and immunomodulator and is a critical element in the coordination between external light stimulation and the body's internal response.
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Affiliation(s)
- Loredana Horodincu
- Preclinics Department, Faculty of Veterinary Medicine, "Ion Ionescu de la Brad" Iasi University of Life Sciences, Mihail Sadoveanu Alley, 700489 Iasi, Romania
| | - Carmen Solcan
- Preclinics Department, Faculty of Veterinary Medicine, "Ion Ionescu de la Brad" Iasi University of Life Sciences, Mihail Sadoveanu Alley, 700489 Iasi, Romania
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Li Y, Hung SW, Zhang R, Man GCW, Zhang T, Chung JPW, Fang L, Wang CC. Melatonin in Endometriosis: Mechanistic Understanding and Clinical Insight. Nutrients 2022; 14:nu14194087. [PMID: 36235740 PMCID: PMC9572886 DOI: 10.3390/nu14194087] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Revised: 09/27/2022] [Accepted: 09/27/2022] [Indexed: 11/16/2022] Open
Abstract
Endometriosis is defined as the development of endometrial glands and stroma outside the uterine cavity. Pathophysiology of this disease includes abnormal hormone profiles, cell survival, migration, invasion, angiogenesis, oxidative stress, immunology, and inflammation. Melatonin is a neuroendocrine hormone that is synthesized and released primarily at night from the mammalian pineal gland. Increasing evidence has revealed that melatonin can be synthesized and secreted from multiple extra-pineal tissues where it regulates immune response, inflammation, and angiogenesis locally. Melatonin receptors are expressed in the uterus, and the therapeutic effects of melatonin on endometriosis and other reproductive disorders have been reported. In this review, key information related to the metabolism of melatonin and its biological effects is summarized. Furthermore, the latest in vitro and in vivo findings are highlighted to evaluate the pleiotropic functions of melatonin, as well as to summarize its physiological and pathological effects and treatment potential in endometriosis. Moreover, the pharmacological and therapeutic benefits derived from the administration of exogenous melatonin on reproductive system-related disease are discussed to support the potential of melatonin supplements toward the development of endometriosis. More clinical trials are needed to confirm its therapeutic effects and safety.
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Affiliation(s)
- Yiran Li
- Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Hong Kong 999077, China
| | - Sze-Wan Hung
- Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Hong Kong 999077, China
| | - Ruizhe Zhang
- Center for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Gene Chi-Wai Man
- Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Hong Kong 999077, China
| | - Tao Zhang
- Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Hong Kong 999077, China
| | - Jacqueline Pui-Wah Chung
- Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Hong Kong 999077, China
| | - Lanlan Fang
- Center for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
- Correspondence: (L.F.); (C.-C.W.); Tel.: +86-371-6691-3635 (L.F.); +852-3505-4267 (C.-C.W.)
| | - Chi-Chiu Wang
- Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Hong Kong 999077, China
- Laboratory of Reproduction and Development, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong 999077, China
- School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong 999077, China
- Chinese University of Hong Kong-Sichuan University Joint Laboratory in Reproductive Medicine, The Chinese University of Hong Kong, Hong Kong 999077, China
- Correspondence: (L.F.); (C.-C.W.); Tel.: +86-371-6691-3635 (L.F.); +852-3505-4267 (C.-C.W.)
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Laste G, Silva AAD, Gheno BR, Rychcik PM. Relationship between melatonin and high-risk pregnancy: A review of investigations published between the years 2010 and 2020. Chronobiol Int 2021; 38:168-181. [PMID: 33432828 DOI: 10.1080/07420528.2020.1863975] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The purpose of this review was to search for articles on human studies investigating the relationship between melatonin and high-risk pregnancy. An electronic search was conducted in the MEDLINE and PubMed databases from September 2010 to October 2020. The initial search produced 441 articles in PubMed and 407 in MEDLINE. After sorting the titles and abstracts, and removing duplicates, we had nine articles in PubMed and three in Medline. The results of these studies mainly show that the association between melatonin receptor 1B polymorphisms and gestational diabetes mellitus is the most common physiological mechanism relating to melatonin and high-risk pregnancy in this review. In addition, the circadian rhythm, decreased melatonin production, and anti-inflammatory and antioxidant effects were explored. The findings of our review of the literature suggest that this indoleamine is essential in high-risk pregnancy for its potent anti-inflammatory and antioxidant effects, regulation of the circadian rhythm, and genic receptor expression.
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Affiliation(s)
- Gabriela Laste
- Programa de Pós-Graduação em Ciências Médicas, Universidade do Vale do Taquari - Univates , Lajeado, Brasil
| | - André Anjos da Silva
- Programa de Pós-Graduação em Ciências Médicas, Universidade do Vale do Taquari - Univates , Lajeado, Brasil
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Kumar N, Singh NK. "Emerging role of Novel Seminal Plasma Bio-markers in Male Infertility: A Review". Eur J Obstet Gynecol Reprod Biol 2020; 253:170-179. [PMID: 32871440 DOI: 10.1016/j.ejogrb.2020.08.015] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2019] [Revised: 07/28/2020] [Accepted: 08/21/2020] [Indexed: 02/03/2023]
Abstract
Male infertility has emerged as an important cause of infertility worldwide. There are many factors affecting male fertility and research is going on to know impact of various factors on sperm functions. Semen analysis is gold standard diagnostic test for male infertility, but it is crude method for estimation of male infertility as seminal composition gets affected by environmental factors, infections, other pathologies, hence, results of semen analysis either becomes normal/ambiguous, leading to failure of diagnosis and delayed treatment. Hence, with need of newer, better tests for assessing male factor infertility, seminal plasma is being tested for biomarkers. Seminal plasma is considered gold mine for male fertility as it contains molecules from male reproductive glands which play important role in sperm function. Study of seminal plasma molecules can give an idea about sperm concentration, motility, morphology and cause of infertility and can serve as biomarkers for male infertility. Present review briefs on some of these novel seminal plasma biomarkers which may play significant role in male fertility and can be used in future for better identification, assessment of infertile males. METHODOLOGY Literature from 1985 to 2019 was searched from various databases including PUBMED, SCOPUS, Google Scholar on seminal plasma biomarkers using keywords: "seminal plasma protein biomarkers", "novel seminal plasma markers and male infertility", "hormones in seminal plasma and male infertility", "oxidative stress and male infertility", "Reactive Oxygen Species and sperm DNA", "immunoinfertility". INCLUSION CRITERIA All full length original or review articles or abstracts on seminal plasma markers and male infertility published in English language in various peer-reviewed journals were considered. EXCLUSION CRITERIA Articles published in languages other than English were excluded from the study. RESULTS Seminal plasma is a big reservoir of molecules derived from the various male reproductive glands which can be used as potential biomarkers of male fertility. CONCLUSION Hence, seminal plasma biomarkers can be used in future for better assessment of male factor infertility, its causes and may play an important role in management of male factor infertility.
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Affiliation(s)
- Naina Kumar
- Department of Obstetrics and Gynecology, All India Institute of Medical Sciences, Mangalagiri, 522503, Guntur, Andhra Pradesh, India.
| | - Namit Kant Singh
- Department of Otorhinolaryngology, Katuri Medical College and Hospital, Guntur, Andhra Pradesh, India.
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Abstract
Insomnia poses significant challenges to public health. It is a common condition associated with marked impairment in function and quality of life, psychiatric and physical morbidity, and accidents. As such, it is important that effective treatment is provided in clinical practice. To this end, this paper reviews critical aspects of the assessment of insomnia and the available treatment options. These options include both non-medication treatments, most notably cognitive behavioral therapy for insomnia, and a variety of pharmacologic therapies such as benzodiazepines, "z-drugs", melatonin receptor agonists, selective histamine H1 antagonists, orexin antagonists, antidepressants, antipsychotics, anticonvulsants, and non-selective antihistamines. A review of the available research indicates that rigorous double-blind, randomized, controlled trials are lacking for some of the most commonly administered insomnia therapies. However, there are an array of interventions which have been demonstrated to have therapeutic effects in insomnia in trials with the above features, and whose risk/benefit profiles have been well characterized. These interventions can form the basis for systematic, evidence-based treatment of insomnia in clinical practice. We review this evidence base and highlight areas where more studies are needed, with the aim of providing a resource for improving the clinical management of the many patients with insomnia.
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Affiliation(s)
- Andrew D. Krystal
- Department of PsychiatryUniversity of California San Francisco School of MedicineSan FranciscoCAUSA,Department of NeurologyUniversity of California San Francisco School of MedicineSan FranciscoCAUSA
| | - Aric A. Prather
- Department of PsychiatryUniversity of California San Francisco School of MedicineSan FranciscoCAUSA
| | - Liza H. Ashbrook
- Department of NeurologyUniversity of California San Francisco School of MedicineSan FranciscoCAUSA
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Hematology, plasma biochemistry, and hormonal analysis of captive Louisiana pine snakes (Pituophis ruthveni): effects of intrinsic factors and analytical methodology. ACTA ACUST UNITED AC 2019. [DOI: 10.1007/s00580-019-03030-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
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Liu Y, Yang Y, Li W, Ao H, Zhang Y, Zhou R, Li K. Effects of melatonin on the synthesis of estradiol and gene expression in pig granulosa cells. J Pineal Res 2019; 66:e12546. [PMID: 30586196 DOI: 10.1111/jpi.12546] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2018] [Revised: 11/20/2018] [Accepted: 12/04/2018] [Indexed: 12/18/2022]
Abstract
The interaction of granulosa cells (GCs) with oocytes is important to regulate follicle development. The exogenous melatonin promoting the maturation of oocytes by GCs has been approved in pig, however, the transcriptome profile and the functions of the genes regulated by melatonin in GCs have not yet to be fully characterized. In this study, we found melatonin could stimulate the synthesis of estradiol in pig GCs. The RNA-seq was used to explore the effects of melatonin on gene expression, a total of 89 differentially expressed genes (DEGs) were identified. Gene ontology analysis showed DEGs which associated with regulation of cell proliferation, cell cycle, and anti-apoptosis were significantly enriched. The functions of two DEGs, NOTCH2 and FILIP1L, were studied in pig GCs. The results showed that NOTCH2 inhibited the synthesis of estradiol, but FILIP1L promoted the synthesis of estradiol. Furthermore, inhibiting NOTCH2 in granulosa cells cocultured with cumulus-oocyte-complexes had no obvious effect on the maturation of pig oocyte, but could upregulate the cleavage rate of oocyte. We proved that FILIP1L had no effect on the maturation and cleavage of pig oocytes. Our work deepens the understanding of melatonin's effects on GCs and oocyte. The DEGs we found will be beneficial to reveal mechanisms of melatonin acting on GCs and oocytes and design the pharmacological interventions.
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Affiliation(s)
- Ying Liu
- The State Key Laboratory for Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Yalan Yang
- School of Life Science and Engineering, Foshan University, Foshan, Guangdong, China
| | - Wentong Li
- School of Life Science and Engineering, Foshan University, Foshan, Guangdong, China
| | - Hong Ao
- The State Key Laboratory for Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Yanmin Zhang
- The State Key Laboratory for Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Rong Zhou
- The State Key Laboratory for Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Kui Li
- The State Key Laboratory for Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China
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Melatonin Does Not Affect Progesterone Basal Secretion but Suppresses the Luteinizing Hormone Receptor Expression in Granulosa Cells of the Japanese Quail. J Poult Sci 2017; 54:312-318. [PMID: 32908442 PMCID: PMC7477261 DOI: 10.2141/jpsa.0170052] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
The aim of this study was to evaluate the potential effect of melatonin on progesterone production by granulosa cells of the Japanese quail. For in vitro experiments, granulosa cells were isolated from pre-ovulatory follicles (F1–F3) when the F1 follicles were predicted to be either immature or mature (at 3–6 or 18–21 h after oviposition, respectively). Granulosa cells were cultured for 12 hwithor without melatonin concentration gradients of 0.0001–100 µg/mL, thereby averting luteinizing hormone (LH) stimulation. The concentration of progesterone in culture medium was measured using an enzyme immunoassay. The expression of melatonin receptor subtypes in granulosa cells from F1 follicles was detected by reverse transcription-PCR. The LH receptor (LHCGR) mRNA level in cultured granulosa cells of the F1 follicles was analyzed using quantitative real-time PCR. Six quails were used in each of four groups for in vivo experiments. Eachgroup received intraperitoneal injection of melatonin (0.67 mg/kg body weight) or mock-vehicle at 3 or 18 h after oviposition, respectively. The birds were decapitated to collect serum 3 hlater (at 6 or 21 h after oviposition, respectively). The serum progesterone level was also measured using an enzyme immunoassay. We observed that melatonin receptor subtypes (Mel-1a, 1b, and 1c) were expressed in the granulosa cells of the F1 follicles of the Japanese quail. Melatonin suppresses the LHCGR mRNA expression in granulosa cells of F1 follicles but does not affect the basal secretion of progesterone in cultured granulosa cells of the F1–F3 follicles. In addition, melatonin treatment has no influence on the serum progesterone concentration at 6 h post-oviposition, but suppresses progesterone level 21 h after oviposition in the Japanese quail.
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Yu GM, Isobe N, Maeda T. Protective Effect of Melatonin on LPS-stimulated Granulosa Cells in Japanese Quail. J Poult Sci 2017; 54:319-325. [PMID: 32908443 PMCID: PMC7477264 DOI: 10.2141/jpsa.0170048] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2017] [Accepted: 05/23/2017] [Indexed: 12/29/2022] Open
Abstract
The aim of this study was to evaluate the potential of melatonin to protect cultured granulosa cells from the harmful effects of lipopolysaccharide (LPS) in quail. Granulosa cells isolated from Japanese quails were pretreated with or without melatonin (10 or 100 µg/mL) for 12 hand then incubated for 12 hin the absence or presence of 100 ng/mL LPS. The expression of pro-inflammatory cytokines and chemokine was detected by quantitative real-time PCR. The levels of oxidative stress biomarkers (dityrosine and nitrite) were determined by ELISA and the Griess reaction. Cell viability was quantified using an MTT assay. Additionally, the level of progesterone was measured by ELISA. We found that melatonin decreased LPS-induced expression of IL-1β, IL-6, and IL-8. In addition, melatonin increased the dityrosine level, but suppressed the nitrite level. Finally, melatonin administration increased the viability of LPS-stimulated granulosa cells in vitro. However, progesterone basal secretion was not significantly changed. These results suggest that melatonin protects cultured granulosa cells from LPS-induced inflammatory and oxidative stress damage and provide evidence that melatonin might have therapeutic utility in ovarian follicle infection in Japanese quail.
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Affiliation(s)
- Guang-Min Yu
- Department of Bioresource Science, Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima 739-8528, Japan
| | - Naoki Isobe
- Department of Bioresource Science, Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima 739-8528, Japan
- The Research Center for Animal Science, Hiroshima University, Higashi-Hiroshima 739-8528, Japan
| | - Teruo Maeda
- Department of Bioresource Science, Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima 739-8528, Japan
- The Research Center for Animal Science, Hiroshima University, Higashi-Hiroshima 739-8528, Japan
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Zhang L, Chen F, Cao J, Dong Y, Wang Z, Chen Y. Melatonin modulates monochromatic light-induced melatonin receptor expression in the hypothalamus of chicks. Acta Histochem 2017; 119:733-739. [PMID: 28943001 DOI: 10.1016/j.acthis.2017.09.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2017] [Revised: 09/08/2017] [Accepted: 09/14/2017] [Indexed: 12/01/2022]
Abstract
To study the mechanism of the effect of monochromatic light on physiological function in chicken, a total of 192 newly hatched chicks were randomly divided into intact, sham-operated and pinealectomy groups then exposed to white light (WL), red light (RL), green light (GL) and blue light (BL) using a light-emitting diode (LED) system for two weeks. At P14, the hypothalami were immediately collected for immunohistochemical staining of melatonin receptor subtypes (Mel1a and Mel1b) and detection of Mel1a and Mel1b expressions using RT-PCR and western blot. Immunohistochemical staining of the hypothalamus showed that the Mel1a-ir cells were distributed in the preoptic area (POA), nucleus preopticus periventricularis (POP) and suprachiasmatic nuclei (SCN), and the Mel1b-ir cells were presented in the POA and SCN. Analysis of RT-PCR and western blot showed that the mRNA and protein levels of Mel1a and Mel1b in the hypothalamus of chick exposed to GL were increased by 10.7-29.3%, 9.18-35.9% and 8.97-27.3% compared to those in the chicks exposed to WL (P=0.029-0.002), RL (P=0.027-0.001) and BL (P=0.038-0.007) in the intact group, respectively. After pinealectomy, however, these parameters decreased and there were no significant differences among the WL, RL, GL and BL groups. These findings suggested that melatonin plays a critical role in GL illumination-enhanced Mel1a and Mel1b expressions in the hypothalamus of chicks.
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Affiliation(s)
- Liwei Zhang
- Laboratory of Anatomy of Domestic Animal, College of Animal Medicine, China Agricultural University, Beijing 100193, China
| | - Funing Chen
- Changping Hospital of Integrated Chinese and Western Medicine, Beijing 102208, China
| | - Jing Cao
- Laboratory of Anatomy of Domestic Animal, College of Animal Medicine, China Agricultural University, Beijing 100193, China
| | - Yulan Dong
- Laboratory of Anatomy of Domestic Animal, College of Animal Medicine, China Agricultural University, Beijing 100193, China
| | - Zixu Wang
- Laboratory of Anatomy of Domestic Animal, College of Animal Medicine, China Agricultural University, Beijing 100193, China
| | - Yaoxing Chen
- Laboratory of Anatomy of Domestic Animal, College of Animal Medicine, China Agricultural University, Beijing 100193, China.
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Zhang L, Chen F, Cao J, Dong Y, Wang Z, Hu M, Chen Y. Green light inhibits GnRH-I expression by stimulating the melatonin-GnIH pathway in the chick brain. J Neuroendocrinol 2017; 29. [PMID: 28295740 DOI: 10.1111/jne.12468] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2016] [Revised: 02/18/2017] [Accepted: 03/09/2017] [Indexed: 11/28/2022]
Abstract
To study the mechanism by which monochromatic light affects gonadotrophin-releasing hormone (GnRH) expression in chicken hypothalamus, a total of 192 newly-hatched chicks were divided into intact, sham-operated and pinealectomy groups and exposed to white (WL), red (RL), green (GL) and blue (BL) lights using a light-emitting diode system for 2 weeks. In the GL intact group, the mRNA and protein levels of GnRH-I in the hypothalamus, the mean cell area and mean cell optical density (OD) of GnRH-I-immunoreactive (-ir) cells of the nucleus commissurae pallii were decreased by 13.2%-34.5%, 5.7%-39.1% and 9.9%-17.3% compared to those in the chicks exposed to the WL, RL and BL, respectively. GL decreased these factors related to GnRH-I expression and the effect of GL was not observed in pinealectomised birds. However, the mRNA and protein levels of hypothalamic gonadotrophin-inhibitory hormone (GnIH) and GnIH receptor (GnIHR), the mean cell area and mean cell OD of the GnIH-ir cells of the paraventricularis magnocellularis, and the plasma melatonin concentration in the chicks exposed to GL were increased by 18.6%-49.2%, 21.1%-60.0% and 8.6%-30.6% compared to the WL, RL and BL intact groups, respectively. The plasma melatonin concentration showed a negative correlation with GnRH-I protein and a positive correlation with GnIH and GnIHR proteins. Protein expression of both GnRH-I and GnIHR showed a negative correlation in the hypothalamus. After pinealectomy, GnRH-I expression increased, whereas plasma melatonin concentration, GnIH and GnIHR expression decreased, and there were no significant differences among the WL, RL, GL and BL groups. Double-labelled immunofluorescence showed that GnIH axon terminals were near GnRH-I neurones, some GnRH-I neurones coexpressed with GnIHR and GnIH neurones coexpressed with melatonin receptor subtype quinone reductase 2. These results demonstrate that green light inhibits GnRH-I expression by increasing melatonin secretion and stimulating melatonin receptor-GnIH-GnIH receptor pathway in the chick brain.
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Affiliation(s)
- L Zhang
- Laboratory of Anatomy of Domestic Animal, College of Animal Medicine, China Agricultural University, Beijing, China
| | - F Chen
- Changping Hospital of Integrated Chinese and Western Medicine, Beijing, China
| | - J Cao
- Laboratory of Anatomy of Domestic Animal, College of Animal Medicine, China Agricultural University, Beijing, China
| | - Y Dong
- Laboratory of Anatomy of Domestic Animal, College of Animal Medicine, China Agricultural University, Beijing, China
| | - Z Wang
- Laboratory of Anatomy of Domestic Animal, College of Animal Medicine, China Agricultural University, Beijing, China
| | - M Hu
- College of Animal Medicine, Agricultural University of Hebei, Baoding, China
| | - Y Chen
- Laboratory of Anatomy of Domestic Animal, College of Animal Medicine, China Agricultural University, Beijing, China
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Vitale SG, Rossetti P, Corrado F, Rapisarda AMC, La Vignera S, Condorelli RA, Valenti G, Sapia F, Laganà AS, Buscema M. How to Achieve High-Quality Oocytes? The Key Role of Myo-Inositol and Melatonin. Int J Endocrinol 2016; 2016:4987436. [PMID: 27651794 PMCID: PMC5019888 DOI: 10.1155/2016/4987436] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2016] [Accepted: 08/02/2016] [Indexed: 12/20/2022] Open
Abstract
Assisted reproductive technologies (ART) have experienced growing interest from infertile patients seeking to become pregnant. The quality of oocytes plays a pivotal role in determining ART outcomes. Although many authors have studied how supplementation therapy may affect this important parameter for both in vivo and in vitro models, data are not yet robust enough to support firm conclusions. Regarding this last point, in this review our objective has been to evaluate the state of the art regarding supplementation with melatonin and myo-inositol in order to improve oocyte quality during ART. On the one hand, the antioxidant effect of melatonin is well known as being useful during ovulation and oocyte incubation, two occasions with a high level of oxidative stress. On the other hand, myo-inositol is important in cellular structure and in cellular signaling pathways. Our analysis suggests that the use of these two molecules may significantly improve the quality of oocytes and the quality of embryos: melatonin seems to raise the fertilization rate, and myo-inositol improves the pregnancy rate, although all published studies do not fully agree with these conclusions. However, previous studies have demonstrated that cotreatment improves these results compared with melatonin alone or myo-inositol alone. We recommend that further studies be performed in order to confirm these positive outcomes in routine ART treatment.
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Affiliation(s)
- Salvatore Giovanni Vitale
- Unit of Gynecology and Obstetrics, Department of Human Pathology in Adulthood and Childhood “G. Barresi”, University of Messina, Messina, Italy
| | - Paola Rossetti
- Unit of Diabetology and Endocrino-Metabolic Diseases, Hospital for Emergency Cannizzaro, Catania, Italy
| | - Francesco Corrado
- Unit of Gynecology and Obstetrics, Department of Human Pathology in Adulthood and Childhood “G. Barresi”, University of Messina, Messina, Italy
| | | | - Sandro La Vignera
- Department of Clinical and Experimental Medicine, Research Centre of Motor Activity and Metabolic Rehabilitation in Diabetes (CRAMD), University of Catania, Catania, Italy
| | - Rosita Angela Condorelli
- Department of Clinical and Experimental Medicine, Research Centre of Motor Activity and Metabolic Rehabilitation in Diabetes (CRAMD), University of Catania, Catania, Italy
| | - Gaetano Valenti
- Department of General Surgery and Medical Surgical Specialties, University of Catania, Catania, Italy
| | - Fabrizio Sapia
- Department of General Surgery and Medical Surgical Specialties, University of Catania, Catania, Italy
| | - Antonio Simone Laganà
- Unit of Gynecology and Obstetrics, Department of Human Pathology in Adulthood and Childhood “G. Barresi”, University of Messina, Messina, Italy
| | - Massimo Buscema
- Unit of Diabetology and Endocrino-Metabolic Diseases, Hospital for Emergency Cannizzaro, Catania, Italy
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Abstract
Humans exhibit seasonal variation in a wide variety of behavioral and physiological processes, and numerous investigators have suggested that this might be because we are sensitive to seasonal variation in day length. The evidence supporting this hypothesis is inconsistent. A new hypothesis is offered here—namely, that some humans indeed are seasonally photoresponsive, but others are not, and that individual variation may be the cause of the inconsistencies that have plagued the study of responsiveness to photoperiod in the past. This hypothesis is examined in relation to seasonal changes in the reproductive activity of humans, and it is developed by reviewing and combining five bodies of knowledge: correlations of human birthrates with photoperiod; seasonal changes in the activity of the neuroendocrine pathway that could link photoperiod to gonadal steroid secretion in humans; what is known about photoperiod, latitude, and reproduction of nonhuman primates; documentation of individual variation in photoresponsiveness in rodents and humans; and what is known about the evolutionary ecology of humans.
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Affiliation(s)
- F H Bronson
- Center for Behavioral Neuroendocrinology, University of Texas at Austin, 78712, USA.
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Sharbatoghli M, Rezazadeh Valojerdi M, Bahadori MH, Salman Yazdi R, Ghaleno LR. The Relationship between Seminal Melatonin with Sperm Parameters, DNA Fragmentation and Nuclear Maturity in Intra-Cytoplasmic Sperm Injection Candidates. CELL JOURNAL 2015; 17:547-53. [PMID: 26464827 PMCID: PMC4601876 DOI: 10.22074/cellj.2015.15] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/26/2014] [Accepted: 06/26/2014] [Indexed: 12/21/2022]
Abstract
Objective Melatonin, the chief secretory product of the pineal gland, regulates dynamic
physiological adaptations that occur in seasonally breeding mammals as a response to
changes in daylight hours. Because of the presence of melatonin in semen and the mem-
brane melatonin receptor in spermatozoa, the impact of melatonin on the regulation of
male infertility is still questionable. The aim of this study was to determine the effects of
endogenous melatonin on human semen parameters (sperm concentration, motility and
normal morphology), DNA fragmentation (DF) and nuclear maturity.
Materials and Methods In this clinical prospective study, semen samples from 75 infer-
tile men were routinely analyzed and assessed for melatonin and total antioxidant capac-
ity (TAC) levels using the enzyme-linked immunosorbent assay (ELISA) and colorimetric
assay kits, respectively. DF was examined by the sperm chromatin dispersion (SCD) test.
Acidic aniline blue staining was used to detect chromatin defects in the sperm nuclei.
Results There was no significant correlation between seminal plasma melatonin and
TAC with sperm parameters and nuclear maturity. However, we observed a positive
significant correlation between DF and melatonin level (r=0.273, P<0.05).
Conclusion Melatonin in seminal plasma is positively correlated with damaged sperm
DNA of infertile patients. The mechanism of this phenomenon needs further study.
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Affiliation(s)
- Mina Sharbatoghli
- Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
| | - Mojtaba Rezazadeh Valojerdi
- Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran ; Department of Anatomy, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran
| | - Mohammad Hadi Bahadori
- Department of Anatomy, Faculty of Medical Science, Guilan University of Medical Sciences, Rasht, Iran
| | - Reza Salman Yazdi
- Department of Andrology, Reproductive Biomedicine Rersearch Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
| | - Leila Rashki Ghaleno
- Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
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Dragojevic Dikic S, Jovanovic AM, Dikic S, Jovanovic T, Jurisic A, Dobrosavljevic A. Melatonin: a "Higgs boson" in human reproduction. Gynecol Endocrinol 2015; 31:92-101. [PMID: 25377724 DOI: 10.3109/09513590.2014.978851] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
As the Higgs boson could be a key to unlocking mysteries regarding our Universe, melatonin, a somewhat mysterious substance secreted by the pineal gland primarily at night, might be a crucial factor in regulating numerous processes in human reproduction. Melatonin is a powerful antioxidant which has an essential role in controlling several physiological reactions, as well as biological rhythms throughout human reproductive life. Melatonin, which is referred to as a hormone, but also as an autocoid, a chronobiotic, a hypnotic, an immunomodulator and a biological modifier, plays a crucial part in establishing homeostatic, neurohumoral balance and circadian rhythm in the body through synergic actions with other hormones and neuropeptides. This paper aims to analyze the effects of melatonin on the reproductive function, as well as to shed light on immunological and oncostatic properties of one of the most powerful hormones.
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Piesiewicz A, Kedzierska U, Turkowska E, Adamska I, Majewski PM. Seasonal postembryonic maturation of the diurnal rhythm of serotonin in the chicken pineal gland. Chronobiol Int 2014; 32:59-70. [DOI: 10.3109/07420528.2014.955185] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Bukovetzky E, Haim A. A comparative study of reproductive and metabolic responses to administration of exogenous melatonin and aldosterone in xeric and mesic spiny mice populations. Comp Biochem Physiol A Mol Integr Physiol 2014; 173C:28-34. [PMID: 24674819 DOI: 10.1016/j.cbpa.2014.03.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2013] [Revised: 03/01/2014] [Accepted: 03/16/2014] [Indexed: 11/17/2022]
Abstract
A comparative study of reproduction revealed differences between desert-adapted Acomys russatus and Mediterranean Acomys cahirinus populations with respect to the environmental cues used for reproductive activity. Long day (LD) conditions were noted as initial reproductive cue for both populations. This research is a follow-up affects comparative endocrine and metabolic study in regards to reproduction where LD-acclimated mice were treated with, exogenous aldosterone (ALDO) and melatonin (MLT). Only the reproductive system of A. russatus females was significantly affected by both hormones. In A. cahirinus females, MLT decreased leptin levels, while in A. russatus, a treatment with both hormones increased leptin levels. In A. russatus males, MLT affects both reproductive and metabolic functions. However, in A. cahirinus males, ALDO and MLT treatments caused an increase in leptin levels, and a decrease in free fatty acid (FFA) levels, respectively. Correlations between leptin and FFA in general were affected by both MLT and ALDO treatments in A. russatus males and A. cahirinus females. Our results support the general idea, that although the reproductive system of A. russatus responded to an osmotic stress, in our case expressed by ALDO treatment, which can be considered as an ultimate signal, where, photoperiod changes are an initial signal.
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Affiliation(s)
- Elena Bukovetzky
- Department of Evolutionary and Environmental Biology, University of Haifa, Mount Carmel, Haifa 31905, Israel.
| | - Abraham Haim
- Department of Evolutionary and Environmental Biology, University of Haifa, Mount Carmel, Haifa 31905, Israel; The Israeli Center for Interdisciplinary Studies in Chronobiology, University of Haifa, Mount Carmel, Haifa 31905, Israel.
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Minkel J, Krystal AD. Optimizing the Pharmacologic Treatment of Insomnia: Current Status and Future Horizons. Sleep Med Clin 2013; 8:333-350. [PMID: 24015116 PMCID: PMC3763861 DOI: 10.1016/j.jsmc.2013.06.002] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
A number of medications are available for treating patients with insomnia. These medications include agents approved as insomnia therapies by the U.S. Food and Drug Administration (FDA), agents approved by the FDA for another condition that are used "off-label" to treat insomnia, and agents available "over-the-counter" that are taken by individuals with insomnia. These agents differ in their properties, their safety and efficacy when used for different insomnia patient subtypes, and the available data on their efficacy and safety in these subtypes. As a result, optimizing the medication treatment of insomnia for a given patient requires that the clinician select an agent for use which has characteristics that make it most likely to effectively and safely address the type of sleep difficulty experienced by that individual. This article is intended to assist clinicians and researchers in carrying out this optimization. It begins by reviewing the basic characteristics of the medications used to treat insomnia. This is followed by a review of the fundamental ways that individuals with insomnia may differ and affect the choice of medication therapy. This review includes discussions that illustrate how to best choose a medication based on the characteristics of the available medications, the key differences among insomnia patients, and the available research literature. Lastly, we discuss future directions for the optimizing pharmacologic management of insomnia. It is hoped that the treatment tailoring methods discussed herein serve as a means of improving the clinical management of insomnia and, thus, improve the lives of the many patients who suffer from this common and impairing condition.
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Supplementation with low concentrations of melatonin improves nuclear maturation of human oocytes in vitro. J Assist Reprod Genet 2013; 30:933-8. [PMID: 23737216 DOI: 10.1007/s10815-013-0021-2] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2013] [Accepted: 05/24/2013] [Indexed: 12/15/2022] Open
Abstract
PURPOSE Studies in bovine and porcine have indicated that melatonin (MT) could induce meiotic maturation of immature oocytes in vitro. The object of the current study was to investigate if MT could ameliorate human oocytes maturation during rescue in vitro maturation (IVM). METHODS Two hundred seventy eight germinal vesicle (GV) oocytes and 451 (MI) metaphase I oocytes were vitrified, thawed and then matured in vitro. All the oocytes were randomly allocated into six groups in which the oocytes were cultured in medium supplemented with different concentrations of MT (0, 10(-2), 1, 10(2), 10(4), 10(6) nM) and nuclear maturation was evaluated at 6 h, 12 h, 18 h, 24 h and 48 h of culture. RESULTS The optimal MT concentration for both GV and MI oocytes was 1 nM. At 24 h of culture, nuclear maturation rate of MI oocytes cultured in 1 nM MT medium was significantly higher than other groups (P < 0.05); Nuclear maturation rate of GV oocytes cultured in 1 nM MT medium was also significantly higher than the control group (P < 0.05). On the other hand, decreased nuclear maturation rate was observed in the high MT concentration group (10(6) nM). CONCLUSIONS The current study demonstrated that low concentration of exogenous MT could ameliorate nuclear maturation of human oocyte during rescue IVM, while high concentration of MT presented negative effects.
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Lampiao F, Du Plessis SS. New developments of the effect of melatonin on reproduction. World J Obstet Gynecol 2013; 2:8-15. [DOI: 10.5317/wjog.v2.i2.8] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2013] [Revised: 04/18/2013] [Accepted: 05/10/2013] [Indexed: 02/05/2023] Open
Abstract
In the past decades, a lot of advances in understanding the biochemistry and physiology of the pineal gland have been made. There is evidence that it interacts with many endocrine as well as non-endocrine tissues to influence their metabolic activity modulating many organs and functions. Melatonin is secreted by the pineal gland in the brain and plays an important role in regulating the neuroendocrine system. This hormone is one of the major role players in the regulation of the circadian sleep-wake cycle. It is normally released from the pineal gland during the night in response to environmental changes in light. Studies have shown that melatonin plays a role in the regulation of many reproductive processes such as puberty, gonadal function, and pregnancy. Beside these, melatonin has been shown to be able to directly neutralize a number of free radicals and reactive oxygen and nitrogen species. The main objective of this review is to provide comprehensive information about the new developments in melatonin research regarding its role in reproduction. A review of international scientific literature was done and a question-and-answer format was used in an attempt to convey comprehensive information in a simple manner. This review discusses evidence currently available relating to the effect of melatonin on reproductive processes. It deliberates the mechanism of action of melatonin, its effect on puberty, testicular and ova function, pregnancy, and oxidative stress. A growing body of scientific evidence is suggesting that melatonin plays an important role in reproductive function. It is therefore imperative to highlight the beneficial effects of this hormone in improving the reproductive processes.
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Sainath S, Swetha CH, Reddy PS. What Do We (Need to) Know About the Melatonin in Crustaceans? ACTA ACUST UNITED AC 2013; 319:365-77. [DOI: 10.1002/jez.1800] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2012] [Revised: 03/25/2013] [Accepted: 04/01/2013] [Indexed: 11/06/2022]
Affiliation(s)
- S.B. Sainath
- Department of Biotechnology; Sri Venkateswara University; Tirupati, Andhra Pradesh; India
| | - CH. Swetha
- Department of Biotechnology; Sri Venkateswara University; Tirupati, Andhra Pradesh; India
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Piesiewicz A, Kedzierska U, Adamska I, Usarek M, Zeman M, Skwarlo-Sonta K, Majewski PM. Pineal arylalkylamine N-acetyltransferase (Aanat) gene expression as a target of inflammatory mediators in the chicken. Gen Comp Endocrinol 2012; 179:143-51. [PMID: 22935823 DOI: 10.1016/j.ygcen.2012.08.013] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2012] [Revised: 08/02/2012] [Accepted: 08/10/2012] [Indexed: 01/06/2023]
Abstract
Previously, we demonstrated that experimental peritonitis in chickens was attenuated by treatment with exogenous melatonin, while the developing inflammation decreased pineal AANAT activity. This suggested the existence of a bidirectional relationship between the activated immune system and pineal gland function. The aim of the present study was to identify the step(s) in the chicken pineal melatonin biosynthetic pathway that are affected by inflammation. Peritonitis was evoked by i.p. injection of thioglycollate solution, either 2h after the start, or 2h before the end of the light period, and the animals were sacrificed 4h later. The effect of inflammation on the expression of genes encoding enzymes participating in melatonin biosynthesis in the pineal gland, i.e. tryptophan hydroxylase 1 (Tph1), dopa decarboxylase (Ddc), arylalkylamine N-acetyltransferase (Aanat) and acetylserotonin O-methyltransferase (Asmt), was evaluated by qPCR. The pineal and serum melatonin concentration as well as the content of its precursors in the pineal gland were measured, along with the activity of the relevant biosynthetic enzymes. Developing peritonitis caused an increase in the pineal levels of the Tph1 mRNA during the night and the Asmt mRNA during the day, while nocturnal Aanat transcription was reduced. Both the pineal and serum melatonin level and the pineal content of N-acetylserotonin (NAS) were decreased during the night in birds with peritonitis. The amount and activity of pineal AANAT were significantly reduced, while the activity of HIOMT was increased under these experimental conditions. These results indicate that the observed decrease in MEL biosynthesis in chickens with developing inflammation is a result of transcriptional downregulation of the Aanat gene, followed by reduced synthesis and activity of the encoded enzyme.
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Affiliation(s)
- Aneta Piesiewicz
- Department of Animal Physiology, Faculty of Biology, University of Warsaw, Miecznikowa 1, 02-096 Warsaw, Poland.
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Piesiewicz A, Kedzierska U, Podobas E, Adamska I, Zuzewicz K, Majewski P. Season-dependent Postembryonic Maturation of the Diurnal Rhythm of Melatonin Biosynthesis in the Chicken Pineal Gland. Chronobiol Int 2012; 29:1227-38. [DOI: 10.3109/07420528.2012.719964] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Pinyot A, Nikolovski Z, Bosch J, Segura J, Gutiérrez-Gallego R. On the use of cells or membranes for receptor binding: Growth hormone secretagogues. Anal Biochem 2010; 399:174-81. [DOI: 10.1016/j.ab.2010.01.003] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2009] [Revised: 12/17/2009] [Accepted: 01/06/2010] [Indexed: 11/16/2022]
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Srinivasan V, Spence WD, Pandi-Perumal SR, Zakharia R, Bhatnagar KP, Brzezinski A. Melatonin and human reproduction: shedding light on the darkness hormone. Gynecol Endocrinol 2009; 25:779-85. [PMID: 19905996 DOI: 10.3109/09513590903159649] [Citation(s) in RCA: 62] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Melatonin, N-acetyl-5-methoxytryptamine, is a molecule with diverse physiological functions. This neuro-hormone affects reproductive performance in a wide variety of species. In most animals, but not exclusively all, melatonin has an antigonadotrophic effect. The seasonal changes in the number of hours per day that melatonin is secreted mediate the temporal coupling of reproductive activity to seasonal changes in day-length. These observations stimulated a search for a role for the pineal gland and melatonin in human reproduction. Clinical experience related to this issue has yielded inconclusive and sometimes conflicting results. This article reviews the current available evidence concerning the effects of melatonin on human reproductive processes (e.g., puberty, ovulation, pregnancy, and fertility). Possible reasons for the vagueness and elusiveness of the clinical effects are discussed.
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Fónagy A. Insect timing (rhythms) from the point of view of neuroendocrine effector mechanisms. ACTA ACUST UNITED AC 2009. [DOI: 10.1556/aphyt.44.2009.1.7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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Richardson G, Wang-Weigand S. Effects of long-term exposure to ramelteon, a melatonin receptor agonist, on endocrine function in adults with chronic insomnia. Hum Psychopharmacol 2009; 24:103-11. [PMID: 19090503 DOI: 10.1002/hup.993] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
OBJECTIVE To evaluate the effects of ramelteon, an MT(1)/MT(2) melatonin receptor agonist used to treat insomnia, on endocrine function in adults with chronic insomnia. METHODS This was a double-blind, placebo-controlled, trial of adults (18-45 years) with chronic insomnia. Subjects received either ramelteon 16 mg or placebo nightly for 6 months. Hormonal measures of the thyroid, reproductive, and adrenal axes were analyzed monthly and compared with baseline and placebo values. RESULTS While isolated changes were detected at some time points, there were no consistent statistically significant differences between treatments on measures of thyroid function (total T4, free T4, TSH, and total T3), adrenal function (AM cortisol, and ACTH), or on most reproductive endocrine measures [LH, FSH, estradiol (women), total, and free testosterone (men)]. Prolactin concentrations were increased overall in women in the ramelteon group compared with placebo (p = 0.003). No clinical effects of elevated prolactin were reported; average menstrual cycle length, duration of menses, and ovulation probability did not differ between groups. CONCLUSIONS Long-term exposure to ramelteon 16 mg, a potent melatonin receptor agonist, resulted in mild, transient increase in prolactin, in women only, that were not associated with measurable reproductive effects. There were no consistent changes in other endocrine measures.
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Affiliation(s)
- Gary Richardson
- Henry Ford Hospital, Sleep Disorders and Research Center, Detroit, MI 48202, USA.
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Kang JT, Koo OJ, Kwon DK, Park HJ, Jang G, Kang SK, Lee BC. Effects of melatonin on in vitro maturation of porcine oocyte and expression of melatonin receptor RNA in cumulus and granulosa cells. J Pineal Res 2009; 46:22-8. [PMID: 18494781 DOI: 10.1111/j.1600-079x.2008.00602.x] [Citation(s) in RCA: 149] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Melatonin is a multifunctional molecule that mediates several circadian and seasonal processes in animal reproduction. Melatonin and its metabolites are antioxidants and free radical scavengers. We investigated the effects of melatonin on porcine oocyte maturation and embryo development. We then investigated the local expression of the melatonin receptor 1 (MT1) gene in cumulus cells, granulosa cells, and the oocytes with the reverse transcription-polymerase chain reaction (RT-PCR) method. We further evaluated the antioxidant effects [reactive oxygen species (ROS) levels in cumulus-oocytes complexes] of melatonin supplementation during in vitro maturation (IVM). Compared with control, melatonin supplementation (10 ng/mL) during IVM resulted in a greater proportion of oocytes extruding the polar body (75.6% versus 84.6%). Significantly greater proportion of parthenogenetically activated oocytes developed to blastocysts when the in vitro medium was supplemented with melatonin; however, cleavage frequency and blastocyst cell number were not affected by the treatment. RT-PCR analysis revealed the expression of MT1 gene in cumulus and granulosa cells but not in oocytes. Melatonin-treated oocytes had significantly lower levels of ROS than did control (untreated) oocytes. We conclude that exogenous melatonin has beneficial effects on nuclear and cytoplasmic maturation during porcine IVM. Some of the observed effects may be mediated by receptor binding and while others may have been receptor independent, e.g., direct free radical scavenging.
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Affiliation(s)
- Jung-Taek Kang
- Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Seoul National University, Seoul, Korea
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Wang Y, Peng KM, Li JL, Song H, Li SH, Wei L, Wang JX. Ultrastructure and melatonin 1a receptor distribution in the ovaries of African ostrich chicks. Cytotechnology 2008; 56:187-95. [PMID: 19002857 DOI: 10.1007/s10616-008-9147-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2007] [Accepted: 04/26/2008] [Indexed: 11/27/2022] Open
Abstract
Healthy 90-day-old ostrich chicks were used in the present study. The ultrastructure and melatonin 1a receptor (MT1) distribution in the ovaries of ostrich chicks was observed by transmission electron microscope and light microscope. The results showed that the ostrich chick ovary contained primordial follicles, primary follicles and secondary follicles, but no mature follicles. There are some unique ultrastructural characteristics observed in the secondary follicle, such as the cortical granule, which was located in cytoplasm beside the nucleus and appeared first in the oocyte. The zona radiata appeared in the secondary follicle, and there was an obvious vitelline membrane. There were intraovarian rete, connecting rete, and extraovarian rete in the ovaries of ostrich chicks. This is the first study that provides immunohistochemical evidence for the localization of the melatonin MT1 in the ostrich chick ovary. The germinal epithelium, follicular cell layer of every grade of follicle, cytoplasm of the oocyte and interstitial cells all expressed MT1. The expression of positive immunoreactivity materials was the strongest in the follicular cell layer of the primordial follicle and germinal epithelium, was weaker in the follicular cell layer of the primary follicle and secondary follicle, and was weakest in the oocytes of all grades of follicle. In addition, the extraovarian rete displayed strong positive expression of MT1, while there was no positive expression in the intraovarian rete or connecting rete. The positive expression of MT1 immunoreactivity in the ovary was very strong, implying that the ovary is an important organ for synthesizing MT1.
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Affiliation(s)
- Yan Wang
- Department of Anatomy, Histology and Embryology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China,
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Sato S, Yin C, Teramoto A, Sakuma Y, Kato M. Sexually dimorphic modulation of GABA(A) receptor currents by melatonin in rat gonadotropin-releasing hormone neurons. J Physiol Sci 2008; 58:317-22. [PMID: 18834560 DOI: 10.2170/physiolsci.rp006208] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2008] [Accepted: 07/31/2008] [Indexed: 11/05/2022]
Abstract
Gonadotropin-releasing hormone (GnRH) neurons represent the final output neurons in the central control of reproduction. gamma-Amino butyric acid (GABA), one of the major regulators of GnRH neurons, depolarizes GnRH neurons isolated from adult rats via GABA(A) receptors. The presence of GABA(A) receptors in GnRH neurons has also been demonstrated morphologically. Furthermore, the pineal hormone melatonin is involved in the regulation of reproductive function, including the timing of the luteinizing hormone surge. The suprachiasmatic nucleus and the GABAergic system in the medial preoptic area are considered as possible sites of the action of melatonin. Until now, however, a direct action of melatonin on GnRH neurons has not been reported. Therefore we examined the effect of melatonin on GABA(A) receptor currents in GnRH neurons isolated from GnRH-EGFP transgenic rats by means of perforated patch-clamp experiments. The GABA(A) receptor currents were modulated by melatonin in a sex-specific manner. In GnRH neurons from adult males, melatonin augmented these currents in 67% of the neurons examined, but attenuated the currents in only 19% of them. These modulations were blocked by the melatonin receptor antagonist luzindole, suggesting an involvement of melatonin receptors. The modulation by melatonin was not observed in GnRH neurons isolated from infantile rats. These findings indicate that GABA affects the excitability of GnRH neurons in adult rats through GABA(A) receptors, and that melatonin modifies this excitability via melatonin receptors in a sex-specific manner.
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Affiliation(s)
- Shun Sato
- Department of Physiology, Nippon Medical School, Tokyo 113-8602, Japan
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Kawashima T, Stępińska U, Kuwana T, Olszańska B. Melatonin receptor genes (mel-1a, mel-1b, mel-1c) are differentially expressed in the avian germ line. Mol Reprod Dev 2008; 75:1408-17. [DOI: 10.1002/mrd.20885] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
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Abstract
The fact that the full extent of the function of the pineal gland has not yet been elucidated, has stimulated melatonin research worldwide. This review introduces melatonin's mechanism of action, direct and indirect antioxidant actions as well as the antioxidant properties of its metabolites, 6-hydroxymelatonin (6-OHM) and N-acetyl-N-formyl-5-methoxykynurenamine (AFMK). At present the mechanism of action is proposed to be receptor-, protein- and nonprotein-mediated. From its popular role in the treatment of jetlag, melatonin is now implicated in the reduction of oxidative stess, both as a free radical scavenger and antioxidant. Melatonin's direct scavenging action in respect of the following will be discussed: superoxide anions, hydrogen peroxide, hydroxyl radicals, singlet oxygen, peroxy radicals and nitric oxide/peroxy nitrite anions. In addition melatonin also possesses indirect antioxidant activity and the role of its metabolites, AFMK and 6-OHM will be presented. It is these free radical scavenging and antioxidant properties of melatonin that has shifted the focus from that of merely strengthening circadian rhythms to that of neuroprotectant: a new place in therapy.
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Affiliation(s)
- Deepa S Maharaj
- Faculty of Pharmacy, Rhodes University, P.O. Box 94, Grahamstown, 6140, South Africa
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36
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Wood S, Quinn A, Troupe S, Kingsland C, Lewis-Jones I. Seasonal variation in assisted conception cycles and the influence of photoperiodism on outcome in in vitro fertilization cycles. HUM FERTIL 2007; 9:223-9. [PMID: 17190668 DOI: 10.1080/14647270600806557] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
The effect of seasonality and daylight length on mammalian reproduction leading to spring births has been well established, and is known as photoperiodism. In assisted reproduction there is much greater uncertainty as to the effect of seasonality. This was a 4-year retrospective analysis of 2709 standardised cycles of IVF/ICSI. Data was analysed with regard to the 1642 cycles occurring during the months of extended daylight (Apr-Sept) and those 1067 cycles during winter months of restricted light length (Oct-Mar). The results showed that there was significant improvement in assisted conception outcomes in cycles performed in summer (lighter) months with more efficient ovarian stimulation 766iu v880iu/per oocyte retrieved (p=0.006). There was similarly a significantly improved implantation rate per embryo transferred 11.42% vs 9.35% (p=0.011) and greater clinical pregnancy rate 20% vs 15% (p=0.0033) during summer cycles. This study appears to demonstrate a significant benefit of increased daylight length on outcomes of IVF/ICSI cycles. Whilst the exact mechanism of this is unclear, it would seem probable that melatonin may have actions at multiple sites and on multiple levels of the reproductive tract, and may exert a more profound effect on outcomes of assisted conception cycles than has been previously considered.
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Affiliation(s)
- Simon Wood
- Department of Obstetrics & Gynaecology, Countess of Chester Hospital, Chester, UK
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Wu PW, Cheng YM, Hsieh WT, Wang YH, Wei CY, Chou PT. 7-Azamelatonin: Efficient Synthetic Routes, Excited-State Double Proton Transfer Properties and Biomedical Implications. ChemMedChem 2007; 2:1071-5. [PMID: 17477342 DOI: 10.1002/cmdc.200700043] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
On the basis of a seven-step synthetic route, the total synthesis of 7-azamelatonin, an analogue of melatonin, has been achieved with an overall yield of approximately 9.2%. In aqueous solution, 7-azamelatonin exhibits a unique excited-state double proton transfer (ESDPT) property, resulting in dual emission bands (405 and 560 nm). The ESDPT property makes 7-azamelatonin superb as a potential molecular probe for future bioapplication and for pharmacological research.
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Affiliation(s)
- Pei-Wen Wu
- Department of Chemistry, National Taiwan University, Taipei, 106, Taiwan, ROC
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Wu YH, Zhou JN, Balesar R, Unmehopa U, Bao A, Jockers R, Van Heerikhuize J, Swaab DF. Distribution of MT1 melatonin receptor immunoreactivity in the human hypothalamus and pituitary gland: Colocalization of MT1 with vasopressin, oxytocin, and corticotropin-releasing hormone. J Comp Neurol 2006; 499:897-910. [PMID: 17072839 DOI: 10.1002/cne.21152] [Citation(s) in RCA: 108] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Melatonin is implicated in numerous physiological processes, including circadian rhythms, stress, and reproduction, many of which are mediated by the hypothalamus and pituitary. The physiological actions of melatonin are mainly mediated by melatonin receptors. We here describe the distribution of the melatonin receptor MT1 in the human hypothalamus and pituitary by immunocytochemistry. MT1 immunoreactivity showed a widespread pattern in the hypothalamus. In addition to the area of the suprachiasmatic nucleus (SCN), a number of novel sites, including the paraventricular nucleus (PVN), periventricular nucleus, supraoptic nucleus (SON), sexually dimorphic nucleus, the diagonal band of Broca, the nucleus basalis of Meynert, infundibular nucleus, ventromedial and dorsomedial nucleus, tuberomamillary nucleus, mamillary body, and paraventricular thalamic nucleus were observed to have neuronal MT1 receptor expression. No staining was observed in the nucleus tuberalis lateralis and bed nucleus of the stria terminalis. The MT1 receptor was colocalized with some vasopressin (AVP) neurons in the SCN, colocalized with some parvocellular and magnocellular AVP and oxytocine (OXT) neurons in the PVN and SON, and colocalized with some parvocellular corticotropin-releasing hormone (CRH) neurons in the PVN. In the pituitary, strong MT1 expression was observed in the pars tuberalis, while a weak staining was found in the posterior and anterior pituitary. These findings provide a neurobiological basis for the participation of melatonin in the regulation of various hypothalamic and pituitary functions. The colocalization of MT1 and CRH suggests that melatonin might directly modulate the hypothalamus-pituitary-adrenal axis in the PVN, which may have implications for stress conditions such as depression.
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Affiliation(s)
- Ying-Hui Wu
- Netherlands Institute for Neuroscience, 1105 BA Amsterdam, The Netherlands
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Kumanov P, Tomova A, Isidori A, Nordio M. Altered melatonin secretion in hypogonadal men: clinical evidence. ACTA ACUST UNITED AC 2005; 28:234-40. [PMID: 16048636 DOI: 10.1111/j.1365-2605.2005.00534.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
The pineal gland, through the rhythmic production of melatonin, seems to play an important role in the control of the reproductive function of many vertebrate species. In contrast, the effects of the pineal gland in humans and the relationship between gonadotropins and melatonin secretion are not yet clarified. On the basis of these considerations, the aim of the present study was to clarify whether melatonin serum concentrations were altered in males with different hypothalamo-pituitary-gonadal disturbances, in comparison to normal individuals. We have studied 36 individuals divided into three groups according to their gonadotropin status: normals, hypogonadotropic hypogonadism and hypergonadotropic hypogonadism. They were submitted to blood sample withdrawal at 03.00, 11.00 and 19.00 h for melatonin determination according to a radioimmunological method, without extraction of the sample. The results obtained in the present study suggest the existence of an interaction between the pituitary and the pineal gland. In fact, in the case of hypersecretion of gonadotropins, nocturnal melatonin release is reduced, while night melatonin secretion is increased in the opposite situation (hypogonadotropic hypogonadism). Both these endocrine pathologies are characterized by a reduced sexual steroid secretion; for that reason, this reduction cannot be regarded as responsible for the two opposite dysfunctions of melatonin release. In conclusion, our study shows that darkness-dependent release of melatonin in males with hypogonadotropic hypogonadism is significantly higher in comparison with the healthy men, while it is significantly reduced in patients with hypergonadotropic hypogonadism. A strong significant negative correlation is also found between gonadotropins and melatonin release.
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Affiliation(s)
- Philip Kumanov
- Clinical Center of Endocrinology, Medical University, Sofia, Bulgaria.
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Chattoraj A, Bhattacharyya S, Basu D, Bhattacharya S, Bhattacharya S, Maitra SK. Melatonin accelerates maturation inducing hormone (MIH): induced oocyte maturation in carps. Gen Comp Endocrinol 2005; 140:145-55. [PMID: 15639142 DOI: 10.1016/j.ygcen.2004.10.013] [Citation(s) in RCA: 53] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2004] [Revised: 10/12/2004] [Accepted: 10/21/2004] [Indexed: 11/23/2022]
Abstract
The present communication is an attempt to demonstrate the influence of melatonin on the action of maturation inducing hormone (MIH) on the maturation of oocytes in carps. The oocytes from gravid female major carp Labeo rohita were isolated and incubated separately in Medium 199 containing (a) only MIH (1 microg/ml), (b) only melatonin (at concentrations of 50, 100 or 500 pg/ml), and (c) both melatonin and MIH, but at different time intervals. In the latter group, melatonin was added to the incubating medium either (i) 4 h before addition of MIH, (ii) 2 h before addition of MIH, (iii) co-administered with MIH (0 h interval) or (iv) 2 h after addition of MIH. In each case, oocytes were further incubated for 4, 8, 12 or 16 h post- administration of MIH, and the effects of treatment on oocyte maturation were evaluated by considering the rate (%) of germinal vesicle breakdown (GVBD). Incubation of oocytes in a medium containing only melatonin did not result in GVBD of any oocyte. Nearly all the oocytes underwent GVBD when incubated with MIH for 16 h. Administration of melatonin along with MIH (at 0 h interval) or 2 h after addition of MIH did not result in any significant change in the rate of GVBD compared to that in a medium containing only MIH. However, it was quite interesting to observe that incubation of oocytes with melatonin especially 4 h prior to addition of MIH in the medium, led to an accelerated rate of GVBD in the oocytes. Experiments with the oocytes of another major carp Cyprinus carpio following an identical schedule depicted similar results except a difference in the optimum melatonin dose. In L. rohita, 50 pg/ml melatonin had maximum acceleratory effect on MIH-induced GVBD of oocytes, while it was 100 pg/ml in C. carpio. Further study revealed that pre-incubation with melatonin accelerates the action of MIH on the formation of a complex of two proteins (MPF), a regulatory component called cyclin B and the catalytic component protein kinase known as cyclin-dependent kinase, Cdk1. Densitometric analysis of the immunoblot data collected from the melatonin pre-treated MIH incubated oocytes showed that cyclin B level continued to increase even after 4 h of incubation, and reached the peak after 12 h. Moreover, determination of H1 kinase activity as an indicator of MPF activity in oocytes revealed that melatonin pre-incubation considerably increased MIH stimulation of histone H1 phosphorylation as compared to MIH alone. Thus, the present study demonstrates for the first time that prior incubation with melatonin accelerates the action of MIH on carp oocyte maturation.
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Affiliation(s)
- Asamanja Chattoraj
- Department of Zoology, Visva-Bharati University, Santiniketan 731 235, India
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Obłap R, Olszańska B. Transition from embryonic to adult transcription pattern of serotonin N-acetyltransferase gene in avian pineal gland. Mol Reprod Dev 2004; 67:145-53. [PMID: 14694429 DOI: 10.1002/mrd.10391] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
The study reports the change of transcription pattern of serotonin N-acetyltransferase gene and melatonin receptor genes during ontogenesis of the avian pineal gland. The RT-PCR technique was used to investigate the expression of the arylalkylamine N-acetyltransferase (AA-NAT) and melatonin receptor genes during development of the pineal glands isolated from Japanese quail (Coturnix coturnix japonica) embryos incubated from 3 days on until hatching (17 days), and in some organs (pineal, brain hemisphere, eye, leg, heart) of the 3-day-old quail embryo. It was shown that two phases of AA-NAT expression are observed during pineal gland development. The first, embryonic-type phase, lasts from the beginning until 7-10 days of incubation, and is marked by the presence of two RT-PCR products for AA-NAT: the shorter mature form without intron (238 bp), and the longer form (323 bp) containing an unprocessed intron of 85 bp. The second, adult-type phase is characterized by the presence of a single mature transcript, containing no intron; it starts from 7 to 10 days of incubation and lasts until hatching and in the adult pineal. The duration of this transition time from the embryonic to the adult transcription pattern in the quail pineal gland from 7 to 10 days of incubation we attribute to asynchronic embryo development, because quail chicks usually hatch between the 16th and 19th day of incubation. Analysis of the AA-NAT protein sequences for chick and quail (GeneBank accession no. U 46 502 and AF 007 068, respectively) revealed their perfect homology with the part of protein read from the sequence present in the adult-type phase of the pineal gland (the RT-PCR product of 238 bp). The presence of the intron (in the 323 bp RT-PCR product, accession no. AY 197 460) in the embryonic-phase of the pineal gland changes the reading frame of the mRNA sequence and the hypothetical resulting protein loses its homology with the chick and quail AA-NAT enzyme starting with 105th amino acid of the complete chick AA-NAT protein comprising 205 amino acids (accession no. U 46 502). In the whole embryos at stages 1-8 (according to the Hamburger-Hamilton classification) both RT-PCR products with and without intron were consistently found, and individual tissues from 3-day-old embryos also produced two AA-NAT products, i.e., the expression was of the embryonic-type. At the time of transition from the embryonic to the adult AA-NAT transcription pattern, in 7-11-day-old embryos, all three melatonin receptor transcripts (mel-1a, mel-1b, and mel-1c) were observed in the pineals, without consistent modifications of the band intensity. In the adult pineal, a single mature AA-NAT transcript was present as well as all three melatonin receptor transcripts, usually with preferential expression of the mel-1a band. The transition time from the embryonic to adult AA-NAT expression pattern coincides well with the acquisition of functional activity and the appearance of melatonin synthesis in the embryonic pineal reported for chicken, as related to quail. We suggest that the change in transcription pattern of the AA-NAT gene may reflect another, still unknown mechanism of regulating AA-NAT activity during ontogenesis, at the level of mRNA processing, whose specificity (or not) for embryonic development we wish to establish in the future.
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Affiliation(s)
- Ruslan Obłap
- Institute of Genetics and Animal Breeding, Polish Academy of Science, Jastrzebiec n/Warsaw, Poland
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Tanavde VS, Maitra A. In vitro modulation of steroidogenesis and gene expression by melatonin: a study with porcine antral follicles. Endocr Res 2003; 29:399-410. [PMID: 14682469 DOI: 10.1081/erc-120026946] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
The effects of melatonin on steroidogenesis and gene expression of CYP 11A, CYP 17, and CYP 19 were investigated using a porcine antral follicle culture model. Follicles were cultured with melatonin at doses of 10, 50, and 100 ng/mL in the presence and absence of an optimum dose of luteinizing hormone (LH) (100 ng/mL) for a period of 30 hours. It was found that melatonin stimulated progesterone production both in the presence and absence of LH. Androstenedione production was stimulated by melatonin at the highest dose of 100 ng/mL but melatonin had an inhibitory effect in the presence of LH. Estradiol production was not affected by melatonin alone, while in the presence of LH it showed a bimodal effect. Expression of genes for steroidogenic enzymes specific for the production of progesterone, androstenedione and estradiol (CYP 11A, CYP 17, and CYP 19, respectively) were also analyzed in the theca of follicles cultured with and without LH. Results showed an inhibition of CYP 11A and CYP 17 expression both in the presence and absence of LH. However, the expression of CYP 19 was not affected. Our results indicate that melatonin modulates ovarian theca cell steroidogenesis at the molecular level and this modulation may be mediated by its effects on the transcriptional activity of the steroidogenic enzymes.
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Affiliation(s)
- V S Tanavde
- Department of Molecular Endocrinology, National Institute for Research in Reproductive Health, (ICMR), Mumbai, India
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43
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Oblap R, Olszańska B. Presence and developmental regulation of serotonin N-acetyltransferase transcripts in oocytes and early quail embryos (Coturnix coturnix japonica). Mol Reprod Dev 2003; 65:132-40. [PMID: 12704723 DOI: 10.1002/mrd.10236] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
By RT-PCR two transcripts for arylalkylamine N-acetyltransferase (AA-NAT; serotonin N-acetyltransferase; EC 2.3.1.87), the key enzyme in melatonin synthesis, were found, for the first time, in the oocytes and blastoderms from freshly laid eggs (323- and 238-bp RT-PCR products), and one (238-bp product) in the pineal gland of Japanese quail (Coturnix coturnix japonica). The two products differed by an intron of 85-bp present in the 323-bp band and absent from the 238-bp band. The identity of the products was confirmed by restriction analysis and sequencing. The ratio of the 323:238-bp bands changed during oogenesis from approximately 17:1 in small 3-mm oocytes to approximately 4:1 in immature vitellogenic oocytes and approximately 1:1 in mature, preovulatory oocytes; it was reversed to approximately 0.2:1 in blastoderms from fertile freshly laid eggs, corresponding to embryo of approximately 40,000 cells. It is proposed that the longer 323-bp product, containing an intron, represents a translationally inactive form of the transcript, stored in maternal RNA. The shorter 238-bp product lacking an intron may represent the mature active AA-NAT mRNA found in the pineal gland and in early embryos, and-to a lower proportion-in older oocytes. These data constitute the first direct proof of an intron sequence in maternal RNA of avian oocyte. It is possible that differential processing of the immature mRNA is part of a transcriptional regulation mechanism of AA-NAT activity. A possible role of extrapineal melatonin in early avian development is discussed.
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Affiliation(s)
- Ruslan Oblap
- Institute of Genetics and Animal Breeding, Polish Academy of Science, Jastrzebiec n/Warsaw, 05-552 Poland
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Rozenboim I, Aharony T, Yahav S. The effect of melatonin administration on circulating plasma luteinizing hormone concentration in castrated White Leghorn roosters. Poult Sci 2003; 81:1354-9. [PMID: 12269616 DOI: 10.1093/ps/81.9.1354] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Melatonin (MLT) has a significant role in mammalian reproduction, with little or no effect in birds. In the present study we studied the role of MLT in regulation of luteinizing hormone (LH) secretion in castrated White Leghorn (WL) roosters. In Experiment 1, castrated WL roosters (n = 30) were divided into three groups, and each group (n = 10) was subdivided into two subgroups (n = 5). Birds in one subgroup received an injection of MLT at 5 mg (MLT-5), 20 mg (MLT-20), or 80 mg (MLT-80)/kg BW. Birds in the second subgroup were vehicle-injected and served as controls. Each dose of MLT was administered on a separate day at 1100 h. Blood was sampled 30 min before and 10, 30, 60, and 120 min after MLT or vehicle administration. Ten minutes after MLT administration, a significant reduction in plasma LH was observed in the MLT-20 and -80 groups, i.e., 70.3 +/- 8.3% and 62.2 +/- 4.1% of control values, respectively. In the MLT-80 group, plasma LH further declined to 42.1 +/- 9.7% of control values 60 min after injection. In Experiment 2, 18 castrated WL roosters were divided into three groups of six birds each. Two groups were injected with 80 mg MLT/kg BW at the beginning of the experiment; the second group received an additional dose of 80 mg MLT/ kg BW 140 min after the first injection. The third group was injected twice (as in second group) with vehicle and served as control. Blood was sampled 30 min before and 30, 60, 120, 170, 200, and 240 min after injection. Repeated MLT injection maintained low levels of plasma LH level until the end of the experiment. In Experiment 3, 10 castrated WL roosters were divided into two groups (n = 5). The first group was injected daily, for 10 d, with 80 mg MLT/kg BW, the second group was vehicle-treated and served as a control. At Day 3, there was a significant reduction in plasma LH level in the MLT-treated group, which continued for 7 d. This study demonstrates that, in birds, MLT suppresses LH secretion in a dose- and a time-related manner.
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Affiliation(s)
- I Rozenboim
- Hebrew University of Jerusalem, Faculty of Agriculture, Department of Animal Science, Rehovot, Israel.
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45
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Aste N, Cozzi B, Stankov B, Panzica G. Sexual differences and effect of photoperiod on melatonin receptor in avian brain. Microsc Res Tech 2001; 55:37-47. [PMID: 11596148 DOI: 10.1002/jemt.1154] [Citation(s) in RCA: 21] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Several data suggest that melatonin may influence avian reproduction by acting at the level of the hypothalamic-hypophisial-gonadal axis, and/or on neural circuits controlling reproductive behaviours. The action of melatonin is exerted through specific receptors whose distribution and pharmacological properties have been extensively investigated. This review will focus on the distribution, sexual dimorphism, and dependence upon the photoperiod of melatonin binding sites in avian species with a special emphasis on Japanese quail. Melatonin receptors are widely distributed in avian brain. They are mostly present in the visual pathways of all the investigated species and in the song controlling nuclei of oscine birds. Sexual dimorphism of melatonin binding sites (higher density in males than in females) was detected in some telencephalic nuclei of songbirds, in the visual pathways, and in the preoptic area of quail. The last region plays a key role in the activation of male quail copulatory behaviour and it hosts a large population of gonadotropin-releasing hormone-containing neurons. Sexual dimorphism of melatonin-binding sites in the above-mentioned regions suggests a differential role for this hormone in the modulation of visual perception, gonadotropin production, and seasonally activated behaviours in male and female quail. Further studies are necessary to understand interrelationships among photic cues, gonadal steroids, density, and sexually dimorphic distribution of melatonin receptors.
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Affiliation(s)
- N Aste
- Department of Biochemistry, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192 Japan
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46
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Xi SC, Siu SW, Fong SW, Shiu SY. Inhibition of androgen-sensitive LNCaP prostate cancer growth in vivo by melatonin: association of antiproliferative action of the pineal hormone with mt1 receptor protein expression. Prostate 2001; 46:52-61. [PMID: 11170132 DOI: 10.1002/1097-0045(200101)46:1<52::aid-pros1008>3.0.co;2-z] [Citation(s) in RCA: 59] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Potential involvement of the mt1 receptor in the antiproliferative action of melatonin on androgen-sensitive LNCaP cells, and melatonin-induced modulation of androgen-insensitive PC-3 cell growth, have been reported in vitro. The effects of melatonin on prostate cancer cell proliferation and their association with mt1 receptor expression were investigated in athymic nude mice xenograft models of LNCaP and PC-3 cells. METHODS Daily saline or melatonin (4 microg/g body weight) was given to nude mice before or after tumor cell inoculation. Tumor volume was measured periodically, and expression of PCNA, cyclin A, PSA, and mt1 receptor was assessed by immunohisto(cyto)chemistry and/or Western blotting. RESULTS Melatonin inhibited the growth of LNCaP tumors, without affecting the growth of PC-3 xenografts, in nude mice. It induced significant decreases in the expression of PCNA, cyclin A, and PSA in LNCaP tumors. Expression of mt1 receptor protein was demonstrated in LNCaP cells, but not in PC-3 cells, both in vivo and in vitro. CONCLUSIONS The antiproliferative action of melatonin on LNCaP tumor growth was demonstrated in vivo, and its association with mt1 receptor protein expression suggests the potential involvement of the receptor in the antitumor activity of the pineal gland hormone.
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MESH Headings
- Animals
- Antibodies, Monoclonal
- Antioxidants/pharmacology
- Antioxidants/therapeutic use
- Apoptosis/drug effects
- Blotting, Western
- Cell Division/drug effects
- Cyclin A/analysis
- Gene Expression Regulation, Neoplastic
- Humans
- Image Processing, Computer-Assisted
- Immunohistochemistry
- In Situ Nick-End Labeling
- Male
- Melatonin/pharmacology
- Melatonin/therapeutic use
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Proliferating Cell Nuclear Antigen/analysis
- Prostate-Specific Antigen/analysis
- Prostatic Neoplasms/drug therapy
- Prostatic Neoplasms/pathology
- Receptors, Cell Surface/analysis
- Receptors, Cytoplasmic and Nuclear/analysis
- Receptors, Melatonin
- Tumor Cells, Cultured
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Affiliation(s)
- S C Xi
- Department of Physiology, Faculty of Medicine, University of Hong Kong, Li Shu Fan Building, 5 Sassoon Road, Hong Kong, China
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47
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Abstract
Evidence exists that repeated injections of melatonin in rather large doses inhibit sexual performance in male rats. In contrast, systemic injection of small doses of this hormone stimulates sexual activity of normal male rats. In these experiments, systemic acute administration of melatonin in small doses (10-100 microg/kg) induced the appearance of ejaculations in impotent Wistar male rats that were selected as showing null sexual approach or showing mounts, intromissions but no ejaculations. This effect was partially abolished by the simultaneous peripheral injection of the non-selective melatonin receptor antagonist, luzindole, or by the acute administration of serotonin or of the 5HT(2A) receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), into the amygdala or the ventral hypothalamus. These results suggest that melatonin may stimulate, in a dose-dependent manner, several copulatory parameters of male sexual behavior and may restore sexual activity in impotent animals by interacting with brain receptors, i. e. melatonin and serotonin receptors.
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Affiliation(s)
- F Drago
- Institute of Pharmacology, Faculty of Medicine, University of Catania Medical School, Viale A. Doria 6, 95125 Catania, Italy.
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Zhao H, Poon AM, Pang SF. Pharmacological characterization, molecular subtyping, and autoradiographic localization of putative melatonin receptors in uterine endometrium of estrous rats. Life Sci 2000; 66:1581-91. [PMID: 11261588 DOI: 10.1016/s0024-3205(00)00478-1] [Citation(s) in RCA: 22] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The objective of this study was to determine the biochemical characteristics, subtypes, and localization of melatonin receptors in the rat uterus in estrous stage. Autoradiography with the melatonin ligand, 2-[125I]iodomelatonin, showed that melatonin receptors were localized in the rat uterine endometrium. Binding of 2-[125I]iodomelatonin in crude membrane preparations of rat uterine endometrium in estrous stage was stable, saturable, reversible and of high affinity. Rosenthal analysis yielded an equilibrium dissociation constant (Kd) of 28.9 +/- 3.59 pmol/l (n = 8) and a maximum number of binding sites (Bmax) of 1.6 +/- 0.15 fmol/mg protein (n = 8). The Kd value determined from kinetic analysis was 16.5 +/- 3.02 pmol/l (n = 3). Competition studies using various indoles and neurotransmitters demonstrated that 2-iodomelatonin, melatonin, 6-chloromelatonin, 6-hydroxymelatonin and N-acetylserotonin showed significant inhibition of the 2-[125I]iodomelatonin binding, while the other indole compounds tested had no significant inhibition. The expression of rat uterine endometrial melatonin receptor subtypes was studied by reverse transcription-polymerase chain reaction (RT-PCR) using mt1 and MT2 receptor gene-specific primers. mt1 receptor cDNA was amplified and confirmed by nucleotide sequencing. These findings indicate that mt1 receptors were present in the rat uterine endometrium, and suggest that melatonin plays an integral part in uterine physiology.
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Affiliation(s)
- H Zhao
- Department of Physiology, The University of Hong Kong, China
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