Prenatal glucocorticoid (GC) therapy is an accepted practice in the prevention of respiratory distress syndrome in the neonate. Concerns regarding its use in early gestation and its side effects upon fetal and postnatal growth and metabolism persist. The recent cloning of the obese gene and obese gene receptors (OB-R) has shed some light upon mechanisms by which altered metabolism (anorexic/catabolic) and diminution in growth occurs. To determine if the ob gene (leptin) receptors mediate the growth reducing effects of GC, we intraperitoneally administered 2 doses of 0.3 mg/kg/day dexamethasone (GC) or vehicle (V) beginning d7, d9, d11, d13, d15, d17, and d19 (term ≈21d; n=7/age/group), and examined the binding of125 I-leptin (10-9M), in the presence and absence of 0.6 X 10-6M unlabeled leptin, to the d9, d11, d13, d15, d17, d19, and d21 frozen saggital embryonic liver sections. In addition, postnatal livers were studied on d15 and d30 (n=7/age/group) subsequent to GC or V administration on d19 gestation. Specific 125I-leptin binding was assessed by quantitation of the autoradiographs and phoshoimages by microdensitometry(Molecular Analyst Microdensitometry Program-1.4.1, NIH). GC reduced body weight at all ages (p < 0.001), and increased hepatic 125I-leptin binding at all ages with a maximal 3-fold increase noted at postnatal d15 (p< 0.005). This is in contrast to a 2-fold decline in hepatic125 I-insulin binding (p < 0.01) at postnatal d15, which served as a known control. We conclude that prenatal GC 1] increases hepatic leptin receptors from mid- to late gestation, 2] has a persistent enhancing effect upon postnatal hepatic leptin receptors. We speculate that prenatal GC increases the biological action of leptin peripherally, thereby affecting the metabolic mileu and the growth potential of the fetus and the newborn.
[Supported by NIH-DK46204]
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Parida, S., MacLennan, N., Yan, H. et al. Prenatal Glucocorticoid Induced Fetal and Postnatal Growth Restriction is Mediated by Obese Gene (OB) or Leptin Receptors † 1559. Pediatr Res 43, 266 (1998). https://doi.org/10.1203/00006450-199804001-01581