Postnatal glucocorticoids induce -ENaC formation and regulate glucocorticoid receptors in the preterm rabbit lung

Mustafa, Shamimunisa B., Robert J. DiGeronimo, Jean A. Petershack, Joseph L. Alcorn, and Steven R. Seidner. Postnatal glucocorticoids induce -ENaC formation and regulate glucocorticoid receptors in the preterm rabbit lung. Am J Physiol Lung Cell Mol Physiol 286: L73–L80, 2004. First published August 29, 2003; 10.1152/ajplung.00342.2002.—At birth, lung fluid clearance is coupled to Na transport through epithelial Na channels (ENaC) in the distal lung epithelium. We evaluated the effect of postnatal glucocorticoids (GC) on lung -ENaC expression in preterm 29-day gestational age (GA) fetal rabbits. Postnatal treatment of 29-day GA fetuses with 0.5 mg/kg of dexamethasone (Dex) iv resulted in a 2and 22-fold increase in lung -ENaC mRNA expression compared with salinetreated fetuses after 8 and 16 h, respectively. Lung -ENaC protein levels in Dex-treated fetuses were also elevated compared with salinetreated counterparts. The extravascular lung water (EVLW)/dry lung tissue weight ratios of 29-day GA fetuses treated with either saline or Dex decreased over 24 h compared with that observed at birth; however, at 24 h, the EVLW/dry lung tissue weight ratios of salineand Dex-treated fetuses were similar. Dex-induced -ENaC mRNA and protein levels were attenuated by glucocorticoid receptor (GCR) antagonist RU-486 in fetal distal lung epithelial cells isolated from 29-day GA fetuses, indicating that GC-dependent augmentation of lung -ENaC requires the presence of functional GCR. Lung GCR mRNA expression and protein levels were elevated in 29-day GA fetuses compared with fetuses at earlier GA. Exposure of 29-day GA fetuses to Dex for 16 h caused a 2.1-fold increase in lung GCR mRNA expression, but GCR protein levels were decreased in Dex-treated fetuses after 24 h. We conclude that postnatal treatment of preterm 29-day GA fetal rabbits with GC results in an elevation of lung -ENaC accompanied by an autoregulation of pulmonary GCR.