Immunolocalization of estrogen receptor alpha and beta in gastric epithelium and enteric neurons

A sexual dimorphism in gastric acid secretion has been known for many years , with women secreting less acid (similar to 40%) than men. The mechanisms mediating, this sex difference are unknown. but a role for estrogens is sug gested from animal models. Two estrogen receptor (ER) subtypes, ER alpha an d ER beta, mediate genomic effects of estrogens, and mRNA for both subtypes has been detected in the rat stomach. The objective of this study was to d etermine the cellular distribution of ER alpha and ER beta proteins in the rat stomach. ER alpha and ER beta proteins were detected in nuclei of fundi c parietal cells and epithelial cells in the progenitor zone. In the antrum , several cells were immunoreactive for ER beta in regions containing stern and neuroendocrine cell types but ER alpha protein was not detected in ant ral glands. Both ER alpha and ER beta proteins were expressed in enteric ne urons within the nucleus and cytoplasm, with specific punctate staining for ER alpha in cell bodies and fibers. These studies are the first to show di fferences between ER alpha and ER beta proteins in the epithelial cellular distribution in the fundus and antrum and to detect co-expression in enteri c neurons. These results suggest that estrogens may inhibit gastric acid se cretion via genomic effects in fundic parietal cells through either ER subt ype and in antral neuroendocrine cells via ER beta. Moreover, co-expression of ER alpha and ER beta in enteric neurons indicates that estrogenic effec ts could also be mediated through neurogenic reflexes. Our findings imply t hat direct regulation of multiple cell types by estrogens may contribute to the modulation of gastric functions that have been recognized during the e strous cycle and between the sexes.