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Developmental Control of Plasma Leptin and Adipose Leptin Messenger Ribonucleic Acid in the Ovine Fetus during Late Gestation: Role of Glucocorticoids and Thyroid Hormones

Department of Physiology, Development and Neuroscience (D.M.O., E.B., F.B.P.W., A.L.F., A.J.F.), University of Cambridge, Cambridge CB2 3EG, United Kingdom; School of Animal Biology (D.B.), Faculty of Natural and Agricultural Sciences, University of Western Australia, Perth, Western Australia 6009, Australia; and Obesity and Metabolic Health Group (N.H.), The Rowett Research Institute, Aberdeen AB21 9SB, United Kingdom

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

In developed countries, the increasing incidence of obesity is a serious health problem. Leptin exposure in the perinatal period affects long-term regulation of appetite and energy expenditure, but control of leptin production in utero is unclear. This study investigated perirenal adipose tissue (PAT) and placental leptin expression in ovine fetuses during late gestation and after manipulation of plasma glucocorticoid and thyroid hormone concentrations. Between 130 and 144 d of gestation (term at 145 ± 2 d), plasma leptin and PAT leptin mRNA levels increased in association with increments in plasma cortisol and T₃. Fetal adrenalectomy prevented these developmental changes, and exposure of intact 130 d fetuses to glucocorticoids, by cortisol infusion or maternal dexamethasone treatment, caused premature elevations in plasma leptin and PAT leptin gene expression. Fetal thyroidectomy increased plasma leptin and PAT leptin mRNA abundance, whereas intravenous T₃ infusion to intact 130 d fetuses had no effect on circulating or PAT leptin. Leptin mRNA expression was low in the ovine placenta. Therefore, in the sheep fetus, PAT appears to be a primary source of leptin in the circulation, and leptin gene expression is regulated by both glucocorticoids and thyroid hormones. Developmental changes in circulating and PAT leptin may mediate the maturational effects of cortisol in utero and have long-term consequences for appetite regulation and the development of obesity.

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