Sex differences and effects of oestrogen in rat gastric mucosal defence

Abstract

AIMTo evaluate sex differences and the effects of oestrogen administration in rat gastric mucosal defence.METHODSSex 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.RESULTSThe 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).CONCLUSIONGastric mucosal blood flow is higher in male than in female rats and is reduced in male rats by oestrogen administration.

Food and Sex-Related Impacts on the Pharmacokinetics of a Single-Dose of Ginsenoside Compound K in Healthy Subjects

“…Additionally, the levels and modes of secretion of hormones differ between males and females, therefore, hormones are also thought to play a role in the differences observed between sexes (Li et al, 2013 ). A recent study showed that gastric mucosal blood flow is higher in male than in female rats, and is reduced in male rats by estrogen administration (Shore et al, 2017 ), which lead us to consider whether hormones are involved in the regulation of the disposition of CK. Nevertheless, additional mechanisms could simultaneously be involved, with different effects on blood concentrations of the parent drug and its metabolites.…”

Sex differences in the gastrointestinal tract of rats and the implications for oral drug delivery

“…Another reason could be due to the differences in male and female rat physiology; previous research has shown that oestrogens are inhibitors of the gastric acid secretion whilst testosterone is an inducer [11,12]. However, in a recent study, it was found that males have a higher gastric blood flow than their female counterparts [13]. Oestrogen administration was able to reduce the mean blood flow in the gastric mucosa by 31%…”

Effect of Food and an Animal’s Sex on P-Glycoprotein Expression and Luminal Fluids in the Gastrointestinal Tract of Wistar Rats

“…Overall, no significant sex differences were identified in the pH profile expect for a lower pH in the fundus and antrum in female rats when compared to males (Figure 1). In a recent study, it was found that male rats have a higher gastric blood flow than their female counterparts [29]. Oestrogen administration was found to reduce the mean blood flow in the gastric mucosa by 31% in males; however, it remained largely unchanged in females.…”