Oestrogen upregulates the expression levels and functional activities of duodenal mucosal CFTR and SLC26A6.
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 E2-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.
Department of Gastroenterology, Affiliated Hospital, Zunyi Medical College, Zunyi, China.|Digestive Disease Institute of Guizhou Province, Zunyi, China.|Research Center of Medicine and Biology, Zunyi Medical College, Zunyi, China.
Hai
H
Jin
Department of Gastroenterology, Affiliated Hospital, Zunyi Medical College, Zunyi, China.|Digestive Disease Institute of Guizhou Province, Zunyi, China.|Research Center of Medicine and Biology, Zunyi Medical College, Zunyi, China.
Guorong
G
Wen
Department of Gastroenterology, Affiliated Hospital, Zunyi Medical College, Zunyi, China.|Digestive Disease Institute of Guizhou Province, Zunyi, China.
Shili
S
Deng
Department of Gastroenterology, Affiliated Hospital, Zunyi Medical College, Zunyi, China.|Digestive Disease Institute of Guizhou Province, Zunyi, China.
Shuo
S
Wan
Department of Gastroenterology, Affiliated Hospital, Zunyi Medical College, Zunyi, China.|Digestive Disease Institute of Guizhou Province, Zunyi, China.|Research Center of Medicine and Biology, Zunyi Medical College, Zunyi, China.
Jingyu
J
Xu
Department of Gastroenterology, Affiliated Hospital, Zunyi Medical College, Zunyi, China.|Digestive Disease Institute of Guizhou Province, Zunyi, China.
Xuemei
X
Liu
Department of Gastroenterology, Affiliated Hospital, Zunyi Medical College, Zunyi, China.|Digestive Disease Institute of Guizhou Province, Zunyi, China.
Rui
R
Xie
Department of Gastroenterology, Affiliated Hospital, Zunyi Medical College, Zunyi, China.|Digestive Disease Institute of Guizhou Province, Zunyi, China.|Research Center of Medicine and Biology, Zunyi Medical College, Zunyi, China.
Hui
H
Dong
Department of Gastroenterology, Affiliated Hospital, Zunyi Medical College, Zunyi, China. tuobiguang@aliyun.com.|Digestive Disease Institute of Guizhou Province, Zunyi, China. tuobiguang@aliyun.com.|Research Center of Medicine and Biology, Zunyi Medical College, Zunyi, China. tuobiguang@aliyun.com.
Biguang
B
Tuo
D000328:Adult; D000368:Aged; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D005576:Colforsin / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism*; D004381:Duodenal Ulcer / Q000188:drug therapy / Q000378:metabolism; D004386:Duodenum / Q000187:drug effects* / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D012727:Sex Characteristics; D000076988:Sulfate Transporters; D015854:Up-Regulation / Q000187:drug effects*; D055815:Young Adult
D001639:Bicarbonates; C505032:CFTR protein, human; D004967:Estrogens; D026901:Membrane Transport Proteins; C439529:SLC26A6 protein, human; D000076988:Sulfate Transporters; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D005576:Colforsin; D004958:Estradiol