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

Shamimunisa B Mustafa, Robert J. DiGeronimo, Jean O Petershack, Joseph L. Alcorn, Steven R Seidner

Research output: Contribution to journalArticle

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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 α-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 α-ENaC mRNA expression compared with saline-treated fetuses after 8 and 16 h, respectively. Lung α-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 α-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 α-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 α-ENaC accompanied by an autoregulation of pulmonary GCR.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume286
Issue number1 30-1
StatePublished - Jan 2004

Fingerprint

Epithelial Sodium Channels
Glucocorticoid Receptors
Glucocorticoids
Rabbits
Lung
Fetus
Gestational Age
Dexamethasone
Extravascular Lung Water
Messenger RNA
Proteins
Parturition
Weights and Measures
Mifepristone

Keywords

  • Epithelial sodium channels
  • Respiratory distress syndrome

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology

Cite this

Postnatal glucocorticoids induce α-ENaC formation and regulate glucocorticoid receptors in the preterm rabbit lung. / Mustafa, Shamimunisa B; DiGeronimo, Robert J.; Petershack, Jean O; Alcorn, Joseph L.; Seidner, Steven R.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 286, No. 1 30-1, 01.2004.

Research output: Contribution to journalArticle

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