Estrogen upregulates the expression levels and functional activities of duodenal mucosal CFTR and SLC26A6

The incidence of duodenal ulcer is markedly lower in women than men, but the cause of the gender difference is not clear. The cystic fibrosis transmembrane conductance regulator (CFTR) and the solute linked carrier 26 gene family A6 (SLC26A6) are two key bicarbonate transport proteins to mediate duodenal mucosal bicarbonate secretion which is an important protective factor against acid-induced duodenal injury. This study aimed to investigate the effect of estrogen on the expressions and functional activities of CFTR and SLC26A6 in duodenal mucosa. We found that the expression levels of duodenal CFTR and SLC26A6 were markedly higher in young women of 20–30 years than in young men of 20–30 years and old women and men of 60–70 years. The expression levels of CFTR and SLC26A6 in young women were markedly higher in preovulatory phases than in premenstrual phases, which was consistent with the changes of serum estradiol levels. The further results showed that duodenal CFTR and SLC26A6 expression levels in female mice were markedly decreased after ovariectomy, and the supplement of estradiol reversed the changes of CFTR and SLC26A6. 17β-estradiol increased CFTR and SLC26A6 expression levels of human duodenocytes in experiments in vitro. Functional experiments showed that basal and forskolin- and prostaglandin E₂-stimulated duodenal bicarbonate secretion in ovariectomized mice was markedly decreased, and, likewise, the supplement of 17β-estradiol reversed the changes. In conclusion, endogenous estrogen upregulates the expressions and functional activities of CFTR and SLC26A6 in duodenal mucosa, which could contribute to protecting duodenum and explaining the gender difference of duodenal ulcer prevalence.

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