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Endocrinology Vol. 140, No. 3 1175-1182
Copyright © 1999 by The Endocrine Society

ARTICLES

Central Administration of Leptin to Ovariectomized Ewes Inhibits Food Intake without Affecting the Secretion of Hormones from the Pituitary Gland: Evidence for a Dissociation of Effects on Appetite and Neuroendocrine Function1

Belinda A. Henry, James W. Goding, Warren S. Alexander, Alan J. Tilbrook, Benedict J. Canny, Frank Dunshea, Alexandra Rao, Ashley Mansell and Iain J. Clarke

Prince Henry’s Institute of Medical Research (B.A.H., A.R., I.J.C.), Clayton, Victoria 3168; the Department of Immunology and Pathology, Monash University Medical School (J.W.G.), Prahran, Victoria 3181; the Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital (W.S.A.), Parkville, Victoria 3050; the Department of Physiology, Monash University (A.J.T., B.J.C.), Clayton, Victoria 3168; Victorian Institute of Animal Science (F.D.), Werribee, Victoria 3030; and Swinburne University of Technology (A.M.), Hawthorn, Victoria 3122, Australia

Address all correspondence and requests for reprints to: Dr. Iain J. Clarke, Prince Henry’s Institute of Medical Research, P.O. Box 5152, Clayton, Victoria 3168, Australia. E-mail: iain.clarke{at}med.monash.edu.au

We have studied the effect of leptin on food intake and neuroendocrine function in ovariectomized ewes. Groups (n = 5) received intracerebroventricular infusions of either vehicle or leptin (20 µg/h) for 3 days and were blood sampled over 6 h on days -1, 2, and for 3 h on day 3 relative to the onset of the infusion. The animals were then killed to measure hypothalamic neuropeptide Y expression by in situ hybridization. Plasma samples were assayed for metabolic parameters and pituitary hormones. Food intake was reduced by leptin, but did not change in controls. Leptin treatment elevated plasma lactate and nonesterified fatty acids, but did not affect glucose or insulin levels, indicating a state of negative energy balance that was met by the mobilization of body stores. Pulse analysis showed that the secretion of LH and GH was not affected by leptin treatment, nor were the mean plasma concentrations of FSH, PRL, or cortisol. Expression of messenger RNA for neuropeptide Y in the arcuate nucleus was reduced by the infusion of leptin, primarily due to reduced expression per cell rather than a reduction in the number of cells observed. Thus, the action of leptin to inhibit food intake is dissociated from neuroendocrine function. These results suggest that the metabolic effects of leptin are mediated via neuronal systems that possess leptin receptors rather than via endocrine effects.




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