Estrogen potentiates prostaglandin E₂-stimulated duodenal mucosal HCO₃⁻ secretion in mice

• Published in: American journal of physiology: endocrinology and metabolism 2012-07, Vol.303 (1), p.E111-E121
• Main Authors: Tuo, Biguang, Wen, Guorong, Wang, Xue, Xu, Jingyu, Xie, Rui, Liu, Xuemei, Dong, Hui
• Format: Article
• Language: eng ; jpn
• Subjects: Animals; Bicarbonates - metabolism; Dinoprostone - agonists; Dinoprostone - metabolism; Duodenum - drug effects; Duodenum - metabolism; Duodenum - secretion; Enzyme Inhibitors - pharmacology; Estradiol - chemistry; Estradiol - metabolism; Estrogen Antagonists - pharmacology; Estrogen Receptor alpha - antagonists & inhibitors; Estrogen Receptor alpha - metabolism; Estrous Cycle; Female; In Vitro Techniques; Intestinal Mucosa - drug effects; Intestinal Mucosa - metabolism; Intestinal Mucosa - secretion; Male; Mice; Phosphatidylinositol 3-Kinase - antagonists & inhibitors; Phosphatidylinositol 3-Kinase - metabolism; Phosphorylation; Protein Processing, Post-Translational; Proto-Oncogene Proteins c-akt - metabolism; Secretory Pathway - drug effects; Sex Characteristics; Signal Transduction - drug effects
• ISSN: 1522-1555
• DOI: 10.1152/ajpendo.00575.2011

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.