Effect Of Estrogen On Duodenal Mucosal Bicarbonate Secretion In Mice And Its Mechanisms

Objective:To examine effect of estrogen on DMBS in mice and its mechanisms. Methods:The experiments were performed in C57BL/6 mice.Duodenal mucosa was stripped of seromuscular layers and mounted in Ussing chambers.DMBS was determined by the pH star technique.The expression of estrogen receptor(ER)αandβin duodenal mucosa was analyzed by western blot.Results:Estrogen (17-β-estradiol) markedly stimulated murine DMBS in a dose-dependent manner (from 10^-11M to 10^-5M)(P＜0.01).It had reached maximal response at the concentration of estrogen 10^-7TM.The results in Western Blot analysis found that ERαand ERβwere expressed in murine duodenal mucosa.Both ERα-selective agonist,R, R-tetrahydrochrysene(R,R-THC),and ERβ-selective agonist,diarylpropionitrile (DPN),stimulated DMBS dose-dependently(10^-10M to 10^-5M)(P＜0.01).On the other hand,ERa-selective antagonist,1,3-bis(4-hydroxyphenyl) -4-methyl-5-(4-[2-piperidinylethoxy]phenol) -1H-pyrazole(MPP)(10^-5M),and ERβ-selective antagonist,4-(2-phenyl-5,7-bis[trifluoromethyl]pyrazolo[1,5-a]pyrimidin-3-yl) phenol(PHTPP)(10^-5M) inhibited estrogen(10^-7M)-stimulated DMBS by 55% and72%(P＜0.01)respectively.The results indicated that estrogen may exert its role through both ERαand ERβ.Intracerllular cAMP inhibitor,SQ22536(10^-5M) and Ca²⁺ channel blocker,verapamil(5×10^-5M),inhibited estrogen-stimulated DMBS by 70% and 79%(P＜0.05 and P＜0.01),respectively,whereas intracellular cGMP inhibitor, NS2028(10^-5M) had no significant effects on estrogen-stimulated DMBS(P＞0.05).Conclusion:Estrogen is a potent stimulant of DMBS in mice.ERαand ERβare expressed in murine duodenal mucosa.DMBS induced by estrogen occurred through binding ERαand ERβand activating cAMP-and Ca²⁺-dependent signal pathways.