Jin Hai, Wen Guorong, Deng Shili, Wan Shuo, Xu Jingyu, Liu Xuemei, Xie Rui, Dong Hui, Tuo Biguang
Department of Gastroenterology, Affiliated Hospital, Zunyi Medical College, Zunyi, China.
Digestive Disease Institute of Guizhou Province, Zunyi, China.
Exp Physiol. 2016 Nov 1;101(11):1371-1382. doi: 10.1113/EP085803.
What is the central question of this study? Duodenal ulcer is a common disease. A sex-based difference in the incidence of duodenal ulcer has long been observed clinically, but the cause is unclear. What is the main finding and its importance? Duodenal mucosal bicarbonate secretion is the most important protective factor in duodenal mucosa against acid-induced damage. The cystic fibrosis transmembrane conductance regulator (CFTR) and the solute-linked carrier 26 gene family A6 (SLC26A6) are two key bicarbonate transport proteins that mediate duodenal mucosal bicarbonate secretion. We demonstrate that endogenous oestrogen upregulates the expression levels and functional activities of duodenal mucosal CFTR and SLC26A6, which contributes to the sex difference in the prevalence of duodenal ulcer. The incidence of duodenal ulcer is markedly lower in women than men, but the cause of the sex 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 that mediate duodenal mucosal bicarbonate secretion, which is an important protective factor against acid-induced duodenal injury. The aim of this study was to investigate the effect of oestrogen 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 (20- to 30-year-old) women than in young men and old (60- to 70-year-old) women and men. 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 concentrations. Further results showed that duodenal CFTR and SLC26A6 expression levels in female mice were markedly decreased after ovariectomy, and supplementation with estradiol reversed the changes in 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 E -stimulated duodenal bicarbonate secretion in ovariectomized mice was markedly decreased and, likewise, supplementation with 17β-estradiol reversed the changes. In conclusion, endogenous oestrogen upregulates the expressions and functional activities of CFTR and SLC26A6 in duodenal mucosa, which could contribute to protection of the duodenum and explain the sex difference in the prevalence of duodenal ulcer.
本研究的核心问题是什么？十二指肠溃疡是一种常见疾病。临床上长期观察到十二指肠溃疡发病率存在性别差异，但原因尚不清楚。主要发现及其重要性是什么？十二指肠黏膜碳酸氢盐分泌是十二指肠黏膜抵御酸诱导损伤的最重要保护因素。囊性纤维化跨膜传导调节因子（CFTR）和溶质载体家族26成员A6（SLC26A6）是介导十二指肠黏膜碳酸氢盐分泌的两种关键碳酸氢盐转运蛋白。我们证明内源性雌激素上调十二指肠黏膜CFTR和SLC26A6的表达水平及功能活性，这导致了十二指肠溃疡患病率的性别差异。十二指肠溃疡的发病率女性明显低于男性，但性别差异的原因尚不清楚。囊性纤维化跨膜传导调节因子（CFTR）和溶质载体家族26成员A6（SLC26A6）是介导十二指肠黏膜碳酸氢盐分泌的两种关键碳酸氢盐转运蛋白，而十二指肠黏膜碳酸氢盐分泌是抵御酸诱导十二指肠损伤的重要保护因素。本研究的目的是探讨雌激素对十二指肠黏膜中CFTR和SLC26A6表达及功能活性的影响。我们发现，年轻（20至30岁）女性十二指肠CFTR和SLC26A6的表达水平明显高于年轻男性以及老年（60至70岁）女性和男性。年轻女性在排卵前期CFTR和SLC26A6的表达水平明显高于经前期，这与血清雌二醇浓度的变化一致。进一步结果显示，雌性小鼠卵巢切除后十二指肠CFTR和SLC26A6表达水平明显降低，补充雌二醇可逆转CFTR和SLC26A6的变化。在体外实验中，17β - 雌二醇增加了人十二指肠细胞CFTR和SLC26A6的表达水平。功能实验表明，去卵巢小鼠基础状态下以及在福斯高林和前列腺素E刺激下的十二指肠碳酸氢盐分泌明显减少，同样，补充17β - 雌二醇可逆转这些变化。总之，内源性雌激素上调十二指肠黏膜中CFTR和SLC26A6的表达及功能活性，这可能有助于保护十二指肠，并解释十二指肠溃疡患病率的性别差异。
