Immunolocalization of estrogen receptor α and β in gastric epithelium and enteric neurons

Abstract

A sexual dimorphism in gastric acid secretion has been known for many years, with women secreting less acid (∼40%) than men. The mechanisms mediating this sex difference are unknown, but a role for estrogens is suggested from animal models. Two estrogen receptor (ER) subtypes, ERα and ERβ, mediate genomic effects of estrogens, and mRNA for both subtypes has been detected in the rat stomach. The objective of this study was to determine the cellular distribution of ERα and ERβ proteins in the rat stomach. ERα and ERβ proteins were detected in nuclei of fundic parietal cells and epithelial cells in the progenitor zone. In the antrum, several cells were immunoreactive for ERβ in regions containing stem and neuroendocrine cell types but ERα protein was not detected in antral glands. Both ERα and ERβ proteins were expressed in enteric neurons within the nucleus and cytoplasm, with specific punctate staining for ERα in cell bodies and fibers. These studies are the first to show differences between ERα and ERβ proteins in the epithelial cellular distribution in the fundus and antrum and to detect co-expression in enteric neurons. These results suggest that estrogens may inhibit gastric acid secretion via genomic effects in fundic parietal cells through either ER subtype and in antral neuroendocrine cells via ERβ. Moreover, co-expression of ERα and ERβ in enteric neurons indicates that estrogenic effects could also be mediated through neurogenic reflexes. Our findings imply that direct regulation of multiple cell types by estrogens may contribute to the modulation of gastric functions that have been recognized during the estrous cycle and between the sexes.