Endogenous and exogenous glucocorticoid regulation of ENaC mRNA expression in developing kidney and lung

Lung liquid absorption at birthis crucial for the successful onset of respiration. Na absorption bythe renal collecting duct plays an important role in renal fluid andelectrolyte homeostasis during the early postnatal period. Theepithelial Na channel (ENaC) plays a central role in mediating thesefunctions, and its subunit expression is developmentally regulated in atemporal and tissue specific pattern. Several lines of evidence suggestthat the prenatal increase in circulating glucocorticoids may play animportant role in increasing ENaC expression during maturation. Wetested the role of the prenatal surge using corticotropin-releasinghormone (CRH) knockout (KO) mice. Relative ENaC expression in lungs of KO mice increased at the same rate as in wild-type (WT) mice, butabsolute expression was only 20-30% of WT. In contrast, relative and absolute expression of all three subunits in kidneys was not different between KO and WT mice. Dexamethasone (Dex) increased -ENaC mRNA in fetal lung and kidney explants within 24 h but had different effects on - or -ENaC. Dex increased - and-ENaC in lung, but only after >48 h of exposure, and had no effecton kidney. The results suggest that the kidney metabolizes endogenous glucocorticoids, but the lung does not. Furthermore, the marked difference between lung and kidney responsiveness to glucocorticoids in- and -ENaC expression suggests that factors other than steroids may be important in regulating functional ENaC expression during development.