Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 21, 2017; 23(3): 426-436
Published online Jan 21, 2017. doi: 10.3748/wjg.v23.i3.426
Sex differences and effects of oestrogen in rat gastric mucosal defence
Richard Shore, Håkan Björne, Yoko Omoto, Anna Siemiatkowska, Jan-Åke Gustafsson, Mats Lindblad, Lena Holm
Richard Shore, Mats Lindblad, Department of Clinical Sciences, Intervention and Technology (CLINTEC), Karolinska Institutet, S-14186 Stockholm, Sweden
Richard Shore, Håkan Björne, Function Perioperative Medicine and Intensive Care, Karolinska University Hospital, S-17176 Stockholm, Sweden
Håkan Björne, Department of Physiology and Pharmacology, Karolinska Institutet, S-17177 Stockholm, Sweden
Yoko Omoto, Department of Endocrine and Breast Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine 465 Kajii-cho, Hirokoji Agaru, Kawaramachi-dori, Kamigyo-ku, Kyoto 602-0841, Japan
Anna Siemiatkowska, Lena Holm, Department of Medical Cell Biology, Uppsala University, S-75123 Uppsala, Sweden
Jan-Åke Gustafsson, Center of Nuclear Receptors and Cell Signalling, University of Houston, Houston, TX 77004, United States
Mats Lindblad, Department of Clinical Sciences, Intervention and Technology (CLINTEC), Karolinska Institutet, S-14186 Stockholm, Sweden
Author contributions: Omoto Y, Gustafsson JÅ, Lindblad M and Holm L designed the research; Shore R, Omoto Y, Siemiatkowska A and Holm L performed the research; Björne H, Omoto Y, Lindblad M and Holm L contributed new reagents/analytic tools; Shore R, Björne H, Omoto Y, Lindblad M and Holm L analysed the data; Shore R, Björne H, Omoto Y, Lindblad M and Holm L wrote the paper.
Institutional review board statement: This study was reviewed and approved by the Regional Ethical Committee for Laboratory Animal Experiments in Uppsala.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Regional Ethical Committee for Laboratory Animal Experiments in Uppsala (IACUC protocol number: C288/9).
Conflict-of-interest statement: There are no conflicts of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Richard Shore, MD, Function Perioperative Medicine and Intensive Care, Karolinska University Hospital, Karolinska vägen, S-17176 Stockholm, Sweden. richard.shore@karolinska.se
Telephone: +46-8-51779939 Fax: +46-8-307795
Received: July 1, 2016
Peer-review started: July 1, 2016
First decision: August 8, 2016
Revised: October 5, 2016
Accepted: October 19, 2016
Article in press: October 19, 2016
Published online: January 21, 2017
Processing time: 197 Days and 8.7 Hours
Abstract
AIM

To evaluate sex differences and the effects of oestrogen administration in rat gastric mucosal defence.

METHODS

Sex differences in gastric mucus thickness and accumulation rate, absolute gastric mucosal blood flow using microspheres, the integrity of the gastric mucosal epithelium in response to a chemical irritant and the effects of oestrogen administration on relative gastric mucosal blood flow in an acute setting was assessed in an in vivo rat experimental model. Subsequently, sex differences in the distribution of oestrogen receptors and calcitonin gene related peptide in the gastric mucosa of animals exposed to oestrogen in the above experiments was evaluated using immunohistochemistry.

RESULTS

The absolute blood flow in the GI-tract was generally higher in males, but only significantly different in the corpus part of the stomach (1.12 ± 0.12 mL/min•g in males and 0.51 ± 0.03 mL/min•g in females) (P = 0.002). After removal of the loosely adherent mucus layer the thickness of the firmly adherent mucus layer in males and females was 79 ± 1 µm and 80 ± 3 µm respectively. After 60 min the mucus thickness increased to 113 ± 3 µm in males and 121 ± 3 µm in females with no statistically significant difference seen between the sexes. Following oestrogen administration (0.1 followed by 1 µg/kg•min), mean blood flow in the gastric mucosa decreased by 31% [68 ± 13 perfusion units (PFU)] in males which was significantly different compared to baseline (P = 0.02). In females however, mean blood flow remained largely unchanged with a 4% (5 ± 33 PFU) reduction. The permeability of the gastric mucosa increased to a higher level in females than in males (P = 0.01) after taurocholate challenge. However, the calculated mean clearance increase did not significantly differ between the sexes [0.1 ± 0.04 to 1.1 ± 0.1 mL/min•100 g in males and 0.4 ± 0.3 to 2.1 ± 0.3 mL/min•100 g in females (P = 0.065)]. There were no significant differences between 17β-Estradiol treated males (mean ratio of positive staining ± SEM) (0.06 ± 0.07) and females (0.11 ± 0.11) in the staining of ERα (P = 0.24). Also, there were no significant differences between 17β-Estradiol treated males (0.18 ± 0.21) and females (0.06 ± 0.12) in the staining of ERβ (P = 0.11). Finally, there were no significant differences between 17β-Estradiol treated males (0.04 ± 0.05) and females (0.11 ± 0.10) in the staining of CGRP (P = 0.14).

CONCLUSION

Gastric mucosal blood flow is higher in male than in female rats and is reduced in male rats by oestrogen administration.

Keywords: Sex differences; Gastric mucosal defence; Blood flow; Oestrogen; Gastric physiology; Mucus

Core tip: We report a sex difference in absolute gastric mucosal blood flow using an in vivo rat experimental model. Male rats had approximately twice as high blood flow in the gastric corpus mucosa compared to females. Moreover, relative gastric mucosal blood flow decreased during oestrogen administration in males but not in females and the permeability of the gastric mucosa increased to a higher level in females than in males after taurocholate challenge. However, mean clearance increase, mucus thickness and accumulation rate and the expression of ERα, ERβ or calcitonin gene related peptide in the gastric mucosa did not differ significantly between the sexes.