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Leptin Regulates Pulsatile Luteinizing Hormone and Growth Hormone Secretion in the Sheep¹

Reproductive Sciences Program (S.N., D.L.F.), Departments of Medicine (Y.Z., C.A.J.), Obstetrics and Gynecology (D.L.F.), and Biology (D.L.F.), University of Michigan, Ann Arbor, Michigan 48109; Ann Arbor Veterans Affairs Medical Center (C.A.J.), Ann Arbor, Michigan 48105; and Department of Animal Sciences, University of Missouri (D.K.), Columbia, Missouri 65211

Address all correspondence and requests for reprints to: Dr. Craig A. Jaffe, Division of Endocrinology and Metabolism, 3920 Taubman Center, Box 0354, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0354. E-mail: cjaffe{at}umich.edu

Administration of leptin during reduced nutrition improves reproductive activity in several monogastric species and reverses GH suppression in rodents. Whether leptin is a nutritional signal regulating neuroendocrine control of pituitary function in ruminant species is unclear. The present study examined the control of pulsatile LH and GH secretion in sheep. We determined whether exogenous leptin could prevent either the suppression of pulsatile LH secretion or the enhancement of GH secretion that occur during fasting. Recombinant human met-leptin (rhmet-leptin; 50 µg/kg BW; n = 8) or vehicle (n = 7) was administered sc every 8 h during a 78-h fast to estrogen-treated, castrated yearling males. LH and GH were measured in blood samples collected every 15 min for 6 h before fasting and during the last 6 h of fasting. Leptin was measured both by a universal leptin assay and by an assay specific for ovine leptin. During the fast, endogenous plasma leptin fell from 1.49 ± 0.16 to 1.03 ± 0.13 ng/ml. The average concentration of rhmet-leptin 8 h after leptin administration was 18.0 ng/ml. During fasting, plasma insulin, glucose, and insulin-like growth factor I levels declined, and nonesterified fatty acid concentrations increased similarly in vehicle-treated and leptin-treated animals. In vehicle-treated animals, LH pulse frequency declined markedly during fasting (5.6 ± 0.5 vs. 1.1 ± 0.5 pulses/6 h; fed vs. fasting; P < 0.0001). Leptin treatment prevented the fall in LH pulse frequency (5.0 ± 0.4 vs. 4.9 ± 0.4 pulses/6 h; P = 0.6). Neither fasting nor leptin administration altered GH pulse frequency. Fasting produced a modest increase in mean concentrations of circulating GH in control animals (2.4 ± 0.5 vs. 3.4 ± 0.6 ng/ml; P = 0.04), whereas there was a much greater increase in GH during leptin treatment (2.7 ± 0.6 vs. 8.6 ± 1.6 ng/ml; P = 0.0001). GH pulse amplitudes were also increased by fasting in control (P = 0.04) and leptin-treated sheep (P = 0.007). The finding that exogenous rhmet-leptin regulates LH and GH secretion in sheep indicates that this fat-derived hormone conveys information about nutrition to mechanisms controlling neuroendocrine function in ruminants.

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