Is the fetal lung a mineralocorticoid receptor target organ? Induction of cortisol-regulated genes in the ovine fetal lung, kidney and small intestine.
Bottom Line: Expression of corticosteroid-induced genes in renal cortex increases at term; in small intestine the induction occurs postnatally.In contrast, in lung expression of MR and GR mRNAs were greater at 100 days to term than postnatally and 11 beta-HSD1 peaked at 145 days; the corticosteroid-induced genes also increased prenatally: Sgk-1 and ENaC alpha increased by 120 days, peaking at 145 days, and Na,K-ATPase alpha1 was greatest at 130 days.The expression of high levels of MR and 11 beta-HSD1 in preterm fetal lung suggest low endogenous fetal cortisol may exert actions at the high affinity MR in vivo, leading to increases in expression of sodium channels important in the regulation of lung liquid secretion and reabsorption.
Affiliation: Department of Pharmacodynamics, University of Florida, Gainesville, FL 32610, USA. email@example.comShow MeSH
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Mentions: The pattern of expression of the MR-induced genes was also tissue-specific. Sgk-1 expression was detected at 80 days and increased with gestational age in both lung and kidney. Sgk-1 gene expression was significantly induced in lungs by 120 days gestation and further increased at 145 days, although the magnitude of the increase varied between 3.5- and 38-fold in individual lungs. Sgk-1 mRNA expression remained significantly elevated postnatally, although the magnitude of this increase was also variable among the lambs (fig. 1e). Sgk-1 protein in fetal lungs was significantly increased at days 120–145 of gestation, and was significantly lower in the newborn lamb than in the 120-day lamb (fig. 5e). In contrast, renal cortical expression of Sgk-1 mRNA was not significantly increased until 145 days, and the fold change was much smaller (about 2-fold; fig. 2e). In renal cortex there was no significant change in protein across time, although Sgk-1 protein was greatest in the newborn renal cortex (fig. 6e). In renal medulla, Sgk-1 mRNA increased between 80 and 100 days, but did not increase further with gestational age or postnatally, and there was an increase in Sgk-1 protein at 120 days as compared to 100 days (fig. 7e). Small intestine Sgk1 mRNA increased only postnatally (fig. 4e).
Affiliation: Department of Pharmacodynamics, University of Florida, Gainesville, FL 32610, USA. firstname.lastname@example.org