Estrogen regulation of duodenal bicarbonate secretion and sex-specific protection of human duodenum.
ABSTRACT The reason that women have a lower prevalence of duodenal ulcer is not clear. We investigated whether estrogen regulates human duodenal bicarbonate secretion (DBS) and whether this process accounts for sex differences in the prevalence of duodenal ulcer.
We performed an epidemiologic study to correlate duodenal ulcer prevalence with sex and age. Proximal DBS was measured from healthy subjects. Estrogen-receptor expression was examined in human duodenal mucosa by immunoblot and immunohistochemical analyses.
Among women, the prevalence of duodenal ulcer was significantly lower than among men. The reduced prevalence was greatest among premenopausal women (20-49 y), who were 3.91- to 5.09-fold less likely to develop duodenal ulcers than age-matched men; the difference was reduced to 1.32-fold or less among subjects aged 60 years or older. Premenopausal (20-29 y), but not postmenopausal (60-69 y), women had significantly higher basal and acid-stimulated DBS than the age-matched men. Basal and acid-stimulated DBS in premenopausal women (20-29 y) were significantly higher than in postmenopausal women (60-69 y), whereas there were no significant differences in basal or acid-stimulated DBS between men who were aged 20-29 years or 60-69 years. Serum levels of estradiol changed in parallel with basal and acid-stimulated DBS during the physiological menstrual cycle in premenopausal women. 17β-estradiol-stimulated DBS was independent of age or sex. Estrogen receptors α and β were detected on plasma membranes and in the cytosol of human duodenal epithelial cells.
Estrogen regulates human DBS, which could reduce the risk for duodenal ulcer in women and contribute to sex differences in the prevalence of duodenal ulcer.
Circulation 08/1995; 92(1):5-8. · 14.74 Impact Factor
Article: Gender-specific protection of estrogen against gastric acid-induced duodenal injury: stimulation of duodenal mucosal bicarbonate secretion.[show abstract] [hide abstract]
ABSTRACT: Because human duodenal mucosal bicarbonate secretion (DMBS) protects duodenum against acid-peptic injury, we hypothesize that estrogen stimulates DMBS, thereby attributing to the clinically observed lower incidence of duodenal ulcer in premenopausal women than the age-matched men. We found that basal and acid-stimulated DMBS responses were 1.5 and 2.4-fold higher in female than male mice in vivo, respectively. Acid-stimulated DMBS in both genders was abolished by ICI 182,780 and tamoxifen. Estradiol-17beta (E2) and the selective estrogen receptor (ER) agonists of ERalpha [1,3,5-Tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole] and ERbeta [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(-)/HCO3(-) anion exchanger inhibitor 4,4'-didsothio- cyanostilbene-2, 2'-disulfonic acid, removal of extracellular Cl(-), 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). ERalpha and ERbeta mRNAs and proteins were detected in murine duodenal epithelium of both genders; however, neither ERalpha nor ERbeta mRNA and protein expression levels differed according to gender. E2 rapidly mobilized intracellular calcium in a duodenal epithelial SCBN cell line that expresses ERalpha and ERbeta, 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(-)/HCO3(-) 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.Endocrinology 06/2008; 149(9):4554-66. · 4.46 Impact Factor
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ABSTRACT: Castration in rats caused a reduction in the degree of ulceration produced by indomethacin. Compared with the normal intact male rats, the value of the castrated rats was highly significant (18.42 +/- 0.22 compared with 9.58 +/- 0.17) (P less than 0.01). However, the normal intact male rats had a greater degree of ulceration than the female rats at the pro-oestrous (2.33 +/- 0.13) or oestrous (2.97 +/- 0.12) phases. The ovariectomized rats, however, showed no significant reduction (P greater than 0.01) in mean ulcer score when compared with the di-oestrous female rats. The mean value of peptic activity was very high in ovariectomized rats while it was reduced in intact female rats. The ovariectomized rats were more prone to ulceration than intact female rats although the susceptibility increased in rats at di-oestrus.African journal of medicine and medical sciences 07/1990; 19(2):139-43.