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Estradiol-17\u03b2 (E2) and the selective estrogen receptor (ER) agonists of ER\u03b1 [1,3,5-Tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole] and ER\u03b2 [2,3-bis(4-hydroxyphenyl) propionitrile], but not progesterone, rapidly stimulated ER-dependent murine DMBS in vivo. E2 dose dependently stimulated murine DMBS, which was attenuated by a Cl\u2212\/HCO3\u2212 anion exchanger inhibitor 4,4\u2032-didsothio- cyanostilbene-2, 2\u2032-disulfonic acid, removal of extracellular Cl\u2212, and in cystic fibrosis transmembrane conductance regulator knockout female mice. E2 stimulated murine DMBS in vitro in both genders with significantly greater response in female than male mice (female to male ratio = 4.3). ER\u03b1 and ER\u03b2 mRNAs and proteins were detected in murine duodenal epithelium of both genders; however, neither ER\u03b1 nor ER\u03b2 mRNA and protein expression levels differed according to gender. E2 rapidly mobilized intracellular calcium in a duodenal epithelial SCBN cell line that expresses ER\u03b1 and ER\u03b2, whereas BAPTA-AM abolished E2-stimulated murine DMBS. Thus, our data show that E2 stimulates DMBS via ER dependent mechanisms linked to intracellular calcium, cystic fibrosis transmembrane conductance regulator, and Cl\u2212\/HCO3\u2212 anion exchanger. Gender-associated differences in basal, acid- and E2-stimulated DMBS may have offered a reasonable explanation for the clinically observed lower incidence of duodenal ulcer in premenopausal women than age-matched men.<\/jats:p>","DOI":"10.1210\/en.2007-1597","type":"journal-article","created":{"date-parts":[[2008,5,22]],"date-time":"2008-05-22T20:53:35Z","timestamp":1211489615000},"page":"4554-4566","source":"Crossref","is-referenced-by-count":56,"title":["Gender-Specific Protection of Estrogen against Gastric Acid-Induced Duodenal Injury: Stimulation of Duodenal Mucosal Bicarbonate Secretion"],"prefix":"10.1210","volume":"149","author":[{"given":"Anders","family":"Smith","sequence":"first","affiliation":[{"name":"Departments of Medicine (A.S., C.C., K.H.K., J.C., X.D., H.D.), School of Medicine, University of California San Diego, La Jolla, California 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