title: Mineralocorticoid effects in the late gestation ovine fetal lung.
abstract: This study was designed to determine the effects of corticosteroids at MR in the late-gestation fetal lung. Since both the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR) are expressed at relatively high levels in the fetal lung, endogenous corticosteroids may act at MR as well as GR in the preterm fetal lung. The GR agonist, betamethasone, the MR agonist, aldosterone, or both were infused intravenously for 48 h in ovine fetuses of approximately 130 days gestation. Effects on airway pressures during stepwise inflation of the in situ lung, expression of ENaC alpha (SCNN1A), ENaC beta (SCNN1B), and Na,K ATPase (ATP1A1), and elastin and collagen content were determined after the infusions. We found that aldosterone significantly reduced the airway pressure measured during the initial step in inflation of the lung, although aldosterone had no overall effect on lung compliance, nor did aldosterone induce expression of ENaCα, ENaCβ or Na,K ATPaseα1. Betamethasone significantly increased expression of the epithelial sodium channel (ENaC) subunit mRNAs, and collagen and elastin content in the lungs, although this dose of betamethasone also had no effect on lung compliance. There was no synergy between effects of the MR and GR agonists. Transcriptomic analysis suggested that although aldosterone did not alter genes in pathways related to epithelial sodium transport, aldosterone did alter genes in pathways involved in cell proliferation in the lungs. The results are consistent with corticosteroid-induced fluid reabsorption at birth through GR rather than MR, but suggest that MR facilitates lung maturation, and may contribute to inflation with the first breaths via mechanisms distinct from known aldosterone effects in other epithelia.
authors.affiliation: Department of Pharmacodynamics, University of Florida, Gainesville, Florida, USA Department of Physiology and Functional Genomics, University of Florida, Gainesville, Florida, USA.
authors.forename: Jarret
authors.initials: J
authors.lastname: McCartney
authors.affiliation: Department of Pharmacodynamics, University of Florida, Gainesville, Florida, USA.
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Richards
authors.affiliation: Department of Physiology and Functional Genomics, University of Florida, Gainesville, Florida, USA.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Wood
authors.affiliation: Department of Pharmacodynamics, University of Florida, Gainesville, Florida, USA Department of Physiology and Functional Genomics, University of Florida, Gainesville, Florida, USA.
authors.forename: Maureen
authors.initials: M
authors.lastname: Keller-Wood
keywords: Fetus; glucocorticoid; lung; mineralocorticoid