title: Sex differences and effects of oestrogen in rat gastric mucosal defence.
abstract: OBJECTIVE
  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 anin vivorat 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).
  
  
  CONCLUSIONS
  Gastric mucosal blood flow is higher in male than in female rats and is reduced in male rats by oestrogen administration.
authors.affiliation: Richard Shore, Mats Lindblad, Department of Clinical Sciences, Intervention and Technology (CLINTEC), Karolinska Institutet, S-14186 Stockholm, Sweden.
authors.forename: Richard
authors.initials: R
authors.lastname: Shore
authors.affiliation: Richard Shore, Mats Lindblad, Department of Clinical Sciences, Intervention and Technology (CLINTEC), Karolinska Institutet, S-14186 Stockholm, Sweden.
authors.forename: Håkan
authors.initials: H
authors.lastname: Björne
authors.affiliation: Richard Shore, Mats Lindblad, Department of Clinical Sciences, Intervention and Technology (CLINTEC), Karolinska Institutet, S-14186 Stockholm, Sweden.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Omoto
authors.affiliation: Richard Shore, Mats Lindblad, Department of Clinical Sciences, Intervention and Technology (CLINTEC), Karolinska Institutet, S-14186 Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Siemiatkowska
authors.affiliation: Richard Shore, Mats Lindblad, Department of Clinical Sciences, Intervention and Technology (CLINTEC), Karolinska Institutet, S-14186 Stockholm, Sweden.
authors.forename: Jan-Åke
authors.initials: JÅ
authors.lastname: Gustafsson
authors.affiliation: Richard Shore, Mats Lindblad, Department of Clinical Sciences, Intervention and Technology (CLINTEC), Karolinska Institutet, S-14186 Stockholm, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Lindblad
authors.affiliation: Richard Shore, Mats Lindblad, Department of Clinical Sciences, Intervention and Technology (CLINTEC), Karolinska Institutet, S-14186 Stockholm, Sweden.
authors.forename: Lena
authors.initials: L
authors.lastname: Holm
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism / Q000502:physiology*; D004008:Diclofenac / Q000008:administration & dosage / Q000009:adverse effects; D004848:Epithelium / Q000098:blood supply / Q000187:drug effects; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D004967:Estrogens / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005753:Gastric Mucosa / Q000098:blood supply* / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D023421:Models, Animal; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000378:metabolism / Q000502:physiology*; D012737:Sex Factors; D013656:Taurocholic Acid / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004967:Estrogens; D011960:Receptors, Estrogen; D004008:Diclofenac; D004958:Estradiol; D013656:Taurocholic Acid; D015740:Calcitonin Gene-Related Peptide
keywords: Blood flow; Gastric mucosal defence; Gastric physiology; Mucus; Oestrogen; Sex differences