title: The fetal sheep lung does not respond to cortisol infusion during the late canalicular phase of development.
abstract: The prepartum surge in plasma cortisol concentrations in humans and sheep promotes fetal lung and surfactant system maturation in the support of air breathing after birth. This physiological process has been used to enhance lung maturation in the preterm fetus using maternal administration of betamethasone in the clinical setting in fetuses as young as 24 weeks gestation (term = 40 weeks). Here, we have investigated the impact of fetal intravenous cortisol infusion during the canalicular phase of lung development (from 109- to 116-days gestation, term = 150 ± 3 days) on the expression of genes regulating glucocorticoid (GC) activity, lung liquid reabsorption, and surfactant maturation in the very preterm sheep fetus and compared this to their expression near term. Cortisol infusion had no impact on mRNA expression of the corticosteroid receptors (GC receptor and mineralocorticoid receptor) or HSD11B-2, however, there was increased expression of HSD11B-1 in the fetal lung. Despite this, cortisol infusion had no effect on the expression of genes involved in lung sodium (epithelial sodium channel -α, -β, or -γ subunits and sodium-potassium ATPase-β1 subunit) or water (aquaporin 1, 3, and 5) reabsorption when compared to the level of expression during exposure to the normal prepartum cortisol surge. Furthermore, in comparison to late gestation, cortisol infusion does not increase mRNA expression of surfactant proteins (SFTP-A, -B, and -C) or the number of SFTP-B-positive cells present in the alveolar epithelium, the cells that produce pulmonary surfactant. These data suggest that there may be an age before which the lung is unable to respond biochemically to an increase in fetal plasma cortisol concentrations.
authors.affiliation: Early Origins of Adult Health Research Group, School of Pharmacy & Medical Sciences, Sansom Institute for Health Research, University of South Australia Adelaide, South Australia, Australia, 5001 ; Molecular & Evolutionary Physiology of the Lung Laboratory, School of Pharmacy & Medical Sciences, Sansom Institute for Health Research, University of South Australia Adelaide, South Australia, Australia, 5001.
authors.forename: Erin V
authors.initials: EV
authors.lastname: McGillick
authors.affiliation: Molecular & Evolutionary Physiology of the Lung Laboratory, School of Pharmacy & Medical Sciences, Sansom Institute for Health Research, University of South Australia Adelaide, South Australia, Australia, 5001.
authors.forename: Sandra
authors.initials: S
authors.lastname: Orgeig
authors.affiliation: Early Origins of Adult Health Research Group, School of Pharmacy & Medical Sciences, Sansom Institute for Health Research, University of South Australia Adelaide, South Australia, Australia, 5001.
authors.forename: I Caroline
authors.initials: IC
authors.lastname: McMillen
authors.affiliation: Early Origins of Adult Health Research Group, School of Pharmacy & Medical Sciences, Sansom Institute for Health Research, University of South Australia Adelaide, South Australia, Australia, 5001.
authors.forename: Janna L
authors.initials: JL
authors.lastname: Morrison
keywords: Glucocorticoid; liquid reabsorption; lung; preterm; surfactant