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Endocrinology Vol. 139, No. 11 4652-4662
Copyright © 1998 by The Endocrine Society


ARTICLES

The Stimulatory Effect of Leptin on the Neuroendocrine Reproductive Axis of the Monkey1

Patricia D. Finn, Matthew J. Cunningham, K.-Y. Francis Pau, Harold G. Spies, Donald K. Clifton and Robert A. Steiner

Departments of Physiology and Biophysics (P.D.F., R.A.S.) and Obstetrics and Gynecology (D.K.C., R.A.S.), Graduate Program in Neurobiology and Behavior (M.J.C.), and the Population Center for Research in Reproduction (D.K.C., R.A.S.), University of Washington, Seattle, Washington 98195; and the Department of Reproductive Sciences (K.-Y.F.P., H.G.S.), Oregon Regional Primate Research Center, Beaverton, Oregon 97006

Address all correspondence and requests for reprints to: Dr. Robert A. Steiner, Department of Physiology and Biophysics, Box 357290, University of Washington, Seattle, Washington 98195-7290. E-mail: steiner{at}u.washington.edu

Leptin acts as a metabolic activator of the neuroendocrine reproductive axis in several rodent species, but whether leptin plays a similar role in primates is unknown. To explore this question, we examined the effects of leptin on gonadotropin and testosterone secretion in male rhesus monkeys that were fasted for 2 days. Mean plasma levels of LH and FSH, LH pulse frequency, and LH pulse amplitude were significantly higher in leptin-treated animals compared with saline-treated controls during the second day of the fast. To identify targets for leptin’s action, we used in situ hybridization and computerized imaging to map leptin receptor (Ob-R) messenger RNA (mRNA) distribution. Ob-R mRNA was observed in the anterior pituitary and several areas of the brain, including the arcuate and ventromedial nuclei of the hypothalamus. Ob-R mRNA was coexpressed in both POMC and neuropeptide Y neurons in the arcuate nucleus, whereas little or no coexpression of Ob-R mRNA was evident in GnRH neurons. These results suggest that leptin is a metabolic signal to the reproductive axis in primates and imply that both POMC and neuropeptide Y neurons are involved in mediating leptin’s effects in the brain.




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