title: Estrogen potentiates prostaglandin E₂-stimulated duodenal mucosal HCO₃⁻ secretion in mice.
abstract: The cause of lower prevalence of duodenal ulcer in young women compared with men is largely unknown. We recently found that sex difference in duodenal mucosal HCO₃⁻ secretion existed in humans and mice, but the mechanisms are not clear. Prostaglandin E₂ (PGE₂) is an important endogenous mediator that plays an important role in the regulation of duodenal HCO₃⁻ secretion. Therefore, in the present study, we investigated the effect of estrogen on PGE₂-stimulated duodenal HCO₃⁻ secretion and the underlying mechanisms. The results showed that 17β-estradiol at the physiological concentration (1 nM) had no significant effects on duodenal mucosal HCO₃⁻ secretion or short-circuit current (I(sc)) in mice. However, the pretreatment of 17β-estradiol (1 nM) markedly potentiated PGE₂-stimulated duodenal HCO₃⁻ secretion and I(sc) (P < 0.01 and P < 0.05). Global estrogen receptor (ER) antagonist ICI-182,780 and ERα-specific antagonist MPP, but not the ERβ-specific antagonist PHTPP, abolished estrogen-potentiated PGE₂-stimulated duodenal HCO₃⁻ secretion and I(sc). 17β-Estradiol and PGE₂ additively increased phosphatidylinositol 3-kinase (PI3K) activity and Akt phosphorylation. Wortmannin, a specific PI3K inhibitor, inhibited estrogen-potentiated PGE₂-stimulated duodenal HCO₃⁻ secretion and I(sc). In conclusion, estrogen at the physiological concentration potentiates PGE₂-stimulated duodenal mucosal HCO₃⁻ secretion through the activation of ERα and the PI3K-dependent mechanism, which may contribute to the sex difference in duodenal mucosal HCO₃⁻ secretion and the lower prevalence of duodenal ulcer in young women.
authors.affiliation: Department of Gastroenterology, Affiliated Hospital, Zunyi Medical College, Zunyi, China. tuobiguang@yahoo.com.cn
authors.forename: Biguang
authors.initials: B
authors.lastname: Tuo
authors.forename: Guorong
authors.initials: G
authors.lastname: Wen
authors.forename: Xue
authors.initials: X
authors.lastname: Wang
authors.forename: Jingyu
authors.initials: J
authors.lastname: Xu
authors.forename: Rui
authors.initials: R
authors.lastname: Xie
authors.forename: Xuemei
authors.initials: X
authors.lastname: Liu
authors.forename: Hui
authors.initials: H
authors.lastname: Dong
mesh_terms: D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D015232:Dinoprostone / Q000819:agonists / Q000378:metabolism*; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000737:chemistry / Q000378:metabolism*; D004965:Estrogen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D030762:Estrous Cycle; D005260:Female; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D055571:Secretory Pathway / Q000187:drug effects; D012727:Sex Characteristics; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D001639:Bicarbonates; D004791:Enzyme Inhibitors; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D000081082:Phosphoinositide-3 Kinase Inhibitors; D004958:Estradiol; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D015232:Dinoprostone