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Plasma Leptin Concentration in Fetal Sheep during Late Gestation: Ontogeny and Effect of Glucocorticoids

Department of Physiology (A.J.F., D.S.G., D.A.G., A.L.F.), University of Cambridge, Cambridge CB2 3EG, United Kingdom; and Aberdeen Centre for Energy Regulation and Obesity (L.T., J.C., N.H.), Appetite and Energy Balance Division, Rowett Research Institute, Aberdeen AB21 9SB, United Kingdom

Address all correspondence and requests for reprints to: Dr. Alison J Forhead, Department of Physiology, University of Cambridge, Downing Street, Cambridge CB2 3EG, United Kingdom. E-mail: . ajf1005{at}cam.ac.uk

The ontogeny and developmental control of plasma leptin concentration in the fetus are poorly understood. The present study investigated plasma leptin concentration in chronically catheterized sheep fetuses near term, and in neonatal and adult sheep. The effect of glucocorticoids on plasma leptin in utero was examined by fetal adrenalectomy and exogenous cortisol or dexamethasone infusion. In intact, untreated fetuses studied between 130 and 140 d (term, 145 ± 2 d), plasma leptin concentration increased in association with the prepartum cortisol surge. Positive relationships were observed between plasma leptin in utero and both gestational age and plasma cortisol. Plasma leptin was also inversely correlated with fetal p_aO₂. The ontogenic rise in plasma leptin was abolished by fetal adrenalectomy. In intact fetuses at 123–127 d, plasma leptin was increased by infusions of cortisol (3–5 mg kg^-1d^-1, +127 ± 21%) for 5 d and dexamethasone (45–60 µg kg^-1d^-1, +268 ± 61%) for 2 d. However, the cortisol-induced rise in plasma leptin was transient; by the fifth day of infusion, plasma leptin was restored to within the baseline range. These findings show that, in the sheep fetus, an intact adrenal gland is required for the normal ontogenic rise in plasma leptin near term. Furthermore, fetal treatment with exogenous and endogenous glucocorticoids increases circulating leptin concentration in utero.

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