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: Ling Luo, Jia Deng, Dao-xin Wang, Jing He, Wang Deng
• Journal: Respiratory physiology & neurobiology (Respir Physiol Neurobiol) Vol. 216 Pg. 52-62 (Sep 15 2015) ISSN: 1878-1519 [Electronic] Netherlands
• PMID: 26051998 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Epithelial Sodium Channels
• Glucocorticoids
• Progestins
• Oleic Acid
• Estradiol
• Dexamethasone
• Adrenocorticotropic Hormone
• 11-beta-Hydroxysteroid Dehydrogenase Type 2
• Carbenoxolone

Topics

• 11-beta-Hydroxysteroid Dehydrogenase Type 2 (metabolism)
• Acute Lung Injury (chemically induced, complications, pathology)
• Adrenocorticotropic Hormone (blood)
• Animals
• Animals, Newborn
• Bronchoalveolar Lavage Fluid
• Carbenoxolone (pharmacology)
• Dexamethasone (toxicity)
• Disease Models, Animal
• Epithelial Cells (drug effects)
• Epithelial Sodium Channels (genetics, metabolism)
• Estradiol (pharmacology)
• Female
• Gene Expression Regulation (drug effects)
• Glucocorticoids (blood)
• Lung (metabolism, pathology)
• Male
• Oleic Acid (toxicity)
• Progestins (pharmacology)
• Pulmonary Edema (drug therapy, etiology)
• Rats
• Rats, Sprague-Dawley