title: Postnatal glucocorticoids induce alpha-ENaC formation and regulate glucocorticoid receptors in the preterm rabbit lung.
abstract: 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 alpha-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 2- and 22-fold increase in lung alpha-ENaC mRNA expression compared with saline-treated fetuses after 8 and 16 h, respectively. Lung alpha-ENaC protein levels in Dex-treated fetuses were also elevated compared with saline-treated 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 saline- and Dex-treated fetuses were similar. Dex-induced alpha-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 alpha-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 alpha-ENaC accompanied by an autoregulation of pulmonary GCR.
authors.affiliation: Department of Pediatrics/Division of Neonatology, University of Texas Health Science Center, 7703 Floyd Curl Dr., San Antonio, TX 78229-3900, USA. mustafa@uthscsa.edu
authors.forename: Shamimunisa B
authors.initials: SB
authors.lastname: Mustafa
authors.forename: Robert J
authors.initials: RJ
authors.lastname: DiGeronimo
authors.forename: Jean A
authors.initials: JA
authors.lastname: Petershack
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Alcorn
authors.forename: Steven R
authors.initials: SR
authors.lastname: Seidner
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D053503:Epithelial Sodium Channels; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005865:Gestational Age; D005938:Glucocorticoids / Q000494:pharmacology*; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000196:embryology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D015222:Sodium Channels / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D053503:Epithelial Sodium Channels; D005938:Glucocorticoids; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; C440894:Scnn1a protein, rat; D015222:Sodium Channels; D003907:Dexamethasone