title: Regulation of epithelial sodium channel expression by oestradiol and progestogen in alveolar epithelial cells.
abstract: Oestrogen (E) and progestogen (P) exert regulatory effects on the epithelial Na(+) channel (ENaC) in the kidneys and the colon. However, the effects of E and P on the ENaC and on alveolar fluid clearance (AFC) remain unclear, and the mechanisms of action of these hormones are unknown. In this study, we showed that E and/or P administration increased AFC by more than 25% and increased the expression of the α and γ subunits of ENaC by approximately 35% in rats subjected to oleic acid-induced acute lung injury (ALI). A similar effect was observed in the dexamethasone-treated group. Furthermore, E and/or P treatment inhibited 11β-hydroxysteroid dehydrogenase (HSD) type 2 (11β-HSD2) activity, increased corticosterone expression and decreased the serum adrenocorticotrophic hormone (ACTH) levels. These effects were similar to those observed following treatment with carbenoxolone (CBX), a nonspecific HSD inhibitor. Further investigation showed that CBX further significantly increased AFC and α-ENaC expression after treatment with a low dose of E and/or P. In vitro, E or P alone inhibited 11β-HSD2 activity in a dose-dependent manner and increased α-ENaC expression by at least 50%, and E combined with P increased α-ENaC expression by more than 80%. Thus, E and P may augment the expression of α-ENaC, enhance AFC, attenuate pulmonary oedema by inhibiting 11β-HSD2 activity, and increase the active glucocorticoid levels in vivo and in vitro.
authors.affiliation: Department of Respiratory Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Luo
authors.affiliation: First Department of Internal Medicine, Traditional Chinese Medical Hospital of Jiangbei District, Chongqing, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Deng
authors.affiliation: Department of Respiratory Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address: daoxinwang@126.com.
authors.forename: Dao-xin
authors.initials: DX
authors.lastname: Wang
authors.affiliation: Department of Respiratory Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Respiratory Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Deng
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000378:metabolism; D055371:Acute Lung Injury / Q000139:chemically induced / Q000150:complications / Q000473:pathology*; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D000831:Animals, Newborn; D001992:Bronchoalveolar Lavage Fluid; D002229:Carbenoxolone / Q000494:pharmacology; D003907:Dexamethasone / Q000633:toxicity; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects*; D053503:Epithelial Sodium Channels / Q000235:genetics / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D005938:Glucocorticoids / Q000097:blood; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D019301:Oleic Acid / Q000633:toxicity; D011372:Progestins / Q000494:pharmacology*; D011654:Pulmonary Edema / Q000188:drug therapy / Q000209:etiology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D053503:Epithelial Sodium Channels; D005938:Glucocorticoids; D011372:Progestins; D019301:Oleic Acid; D004958:Estradiol; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D002229:Carbenoxolone
keywords: 11β-Hydroxysteroid dehydrogenase type 2; Acute respiratory distress syndrome; Epithelial Na(+) channel; Oestradiol; Progestogen; acute lung injury