Clinical Research
Copyright ©The Author(s) 2004. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 1, 2004; 10(17): 2529-2534
Published online Sep 1, 2004. doi: 10.3748/wjg.v10.i17.2529
Hematotesticular barrier is altered from early stages of liver cirrhosis: Effect of insulin-like growth factor 1
Inma Castilla-Cortázar, Nieves Diez, María García-Fernández, Juan Enrique Puche, Fernando Diez-Caballero, Jorge Quiroga, Matías Díaz-Sánchez, Alberto Castilla, Amelia Díaz Casares, Isabel Varela-Nieto, Jesús Prieto, Salvador González-Barón
Inma Castilla-Cortázar, Nieves Diez, María García-Fernández, Fernando Diez-Caballero, Matías Díaz-Sánchez, Department of Human Physiology, University of Navarra, Pamplona, Navarra, Spain
Jorge Quiroga, Jesús Prieto, Department of Internal Medicine, Liver Unit, University of Navarra, Pamplona, Navarra, Spain
Inma Castilla-Cortázar, María García-Fernández, Juan Enrique Puche, Amelia Díaz Casares, Salvador González-Barón, Department of Human Physiology, School of Medicine, University of Málaga, Malaga, Spain
Alberto Castilla, Department of Internal Medicine, Hospital Sierrallana, Tollelavega and School of Medicine, University of the Basque Country-Vitoria-Gasteiz, Spain
Isabel Varela-Nieto, Instituto de Investigaciones Biomédicas “Alberto Sols”, Consejo Superior de Investigaciones Cientificas-Universidad Autónoma de Madrid (CSIC-UAM), Madrid, Spain
Author contributions: All authors contributed equally to the work.
Supported by the Spanish Program I + D, SAF 99/0072 and SAF 2001/1672
Correspondence to: Inma Castilla-Cortázar, MD, PhD, Department of Human Physiology, School of Medicine, University of Málaga, Campus Teatinos 29080, Málaga, Spain. iccortazar@uma.es
Telephone: +34-952131577 Fax: +34-952131650
Received: February 6, 2004
Revised: February 24, 2004
Accepted: March 4, 2004
Published online: September 1, 2004
Abstract

AIM: The pathogenesis of hypogonadism in liver cirrhosis is not well understood. Previous results from our laboratory showed that IGF-1 deficiency might play a pathogenetic role in hypogonadism of cirrhosis. The administration of IGF-1 for a short period of time reverted the testicular atrophy associated with advanced experimental cirrhosis. The aim of this study was to establish the historical progression of the described alterations in the testes, explore testicular morphology, histopathology, cellular proliferation, integrity of testicular barrier and hypophyso-gonadal axis in rats with no ascitic cirrhosis.

METHODS: Male Wistar rats with histologically-proven cirrhosis induced with carbon tetrachloride (CCl4) for 11 wk, were allocated into two groups (n = 12, each) to receive recombinant IGF-1 (2 μg/100 g.d, sc) for two weeks or vehicle. Healthy rats receiving vehicle were used as control group (n = 12).

RESULTS: Compared to controls, rats with compensated cirrhosis showed a normal testicular size and weight and very few histopathological testicular abnormalities. However, these animals showed a significant diminution of cellular proliferation and a reduction of testicular transferrin expression. In addition, pituitary-gonadal axis was altered, with significant higher levels of FSH (P < 0.001 vs controls) and increased levels of LH in untreated cirrhotic animals. Interestingly, IGF-1 treatment normalized testicular transferrin expression and cellular proliferation and reduced serum levels of LH (P = ns vs controls, and P < 0.01 vs untreated cirrhotic group).

CONCLUSION: The testicular barrier is altered from an early stage of cirrhosis, shown by a reduction of transferrin expression in Sertoli cells, a diminished cellular proliferation and an altered gonadal axis. The treatment with IGF-1 could be also useful in this initial stage of testicular disorder associated with compensated cirrhosis.

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