A Role for Mineralocorticoid Receptors in the Physiology of the Ovine Fetus: Effects on ACTH and Lung Liquid Composition

Abstract

In the human and ovine fetus, the presence of 11β-hydroxysteroid dehydrogenase 1 allows cortisol and other corticosteroids to act at mineralocorticoid receptors (MRs) in lung and brain. To test the physiologic role of MRs in the late gestation fetus, fetal lambs were infused with a specific MR antagonist for 12 h. Infusion of the MR antagonist significantly increased plasma ACTH and cortisol concentrations. Infusion of the MR antagonist also significantly increased fetal Pco2 and hematocrit, and decreased fetal pH, but did not alter fetal heart rate or blood pressure. Infusion of the MR antagonist altered the ratio of Na⁺ to K⁺ in lung fluid but did not alter the rate of production of lung liquid or the expression of the epithelial sodium channel α or of the Na,K ATPaseα1 in lung. These results suggest that corticosteroids act at MR to regulate ACTH and blood volume and modulate lung fluid composition in the fetus, but basal levels of corticosteroids do not alter lung liquid production rate through effects on MR.