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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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H. Watanobe and S. Habu Leptin Regulates Growth Hormone-Releasing Factor, Somatostatin, and alpha -Melanocyte-Stimulating Hormone But Not Neuropeptide Y Release in Rat Hypothalamus In Vivo: Relation with Growth Hormone Secretion J. Neurosci., July 15, 2002; 22(14): 6265 - 6271. [Abstract] [Full Text] [PDF]
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S. D. Sullivan, L. C. Howard, A. H. Clayton, and S. M. Moenter Serotonergic Activation Rescues Reproductive Function in Fasted Mice: Does Serotonin Mediate the Metabolic Effects of Leptin on Reproduction? Biol Reprod, June 1, 2002; 66(6): 1702 - 1706. [Abstract] [Full Text] [PDF]
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M. J. Cunningham, J. M. Scarlett, and R. A. Steiner Cloning and Distribution of Galanin-Like Peptide mRNA in the Hypothalamus and Pituitary of the Macaque Endocrinology, March 1, 2002; 143(3): 755 - 763. [Abstract] [Full Text] [PDF]
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J. Lado-Abeal, J. D. Veldhuis, and R. L. Norman Glucose Relays Information Regarding Nutritional Status to the Neural Circuits That Control the Somatotropic, Corticotropic, and Gonadotropic Axes in Adult Male Rhesus Macaques Endocrinology, February 1, 2002; 143(2): 403 - 410. [Abstract] [Full Text] [PDF]
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F. H. Koegler, K. L. Grove, A. Schiffmacher, M. S. Smith, and J. L. Cameron Central Melanocortin Receptors Mediate Changes in Food Intake in the Rhesus Macaque Endocrinology, June 1, 2001; 142(6): 2586 - 2592. [Abstract] [Full Text] [PDF]
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P. Magni, L. Martini, and M. Motta Leptin Actions on the Reproductive Axis J. Clin. Endocrinol. Metab., February 1, 2001; 86(2): 946a - 947. [Full Text]
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P. D. Finn, M. J. Cunningham, D. G. Rickard, D. K. Clifton, and R. A. Steiner Serotonergic Neurons Are Targets for Leptin in the Monkey J. Clin. Endocrinol. Metab., January 1, 2001; 86(1): 422 - 426. [Abstract] [Full Text]
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R. R. González, P. Caballero-Campo, M. Jasper, A. Mercader, L. Devoto, A. Pellicer, and C. Simon Leptin and Leptin Receptor Are Expressed in the Human Endometrium and Endometrial Leptin Secretion Is Regulated by the Human Blastocyst J. Clin. Endocrinol. Metab., December 1, 2000; 85(12): 4883 - 4888. [Abstract] [Full Text]
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S. Nagatani, Y. Zeng, D. H. Keisler, D. L. Foster, and C. A. Jaffe Leptin Regulates Pulsatile Luteinizing Hormone and Growth Hormone Secretion in the Sheep Endocrinology, November 1, 2000; 141(11): 3965 - 3975. [Abstract] [Full Text] [PDF]
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Z. Atcha, F. R. A. Cagampang, J. A. Stirland, I. D. Morris, A. N. Brooks, F. J. P. Ebling, M. Klingenspor, and A. S. I. Loudon Leptin Acts on Metabolism in a Photoperiod-Dependent Manner, But Has No Effect on Reproductive Function in the Seasonally Breeding Siberian Hamster (Phodopus sungorus) Endocrinology, November 1, 2000; 141(11): 4128 - 4135. [Abstract] [Full Text] [PDF]
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M. C. Henson and V. D. Castracane Leptin in Pregnancy Biol Reprod, November 1, 2000; 63(5): 1219 - 1228. [Abstract] [Full Text]
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T. Tanaka, S. Nagatani, D. C. Bucholtz, S. Ohkura, H. Tsukamura, K.-I. Maeda, and D. L. Foster Central Action of Insulin Regulates Pulsatile Luteinizing Hormone Secretion in the Diabetic Sheep Model Biol Reprod, May 1, 2000; 62(5): 1256 - 1261. [Abstract] [Full Text]
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C. S.Mantzoros, D. W.Cramer, R. F.Liberman, and R. L.Barbieri Predictive value of serum and follicular fluid leptin concentrations during assisted reproductive cycles in normal women and in women with the polycystic ovarian syndrome Hum. Reprod., March 1, 2000; 15(3): 539 - 544. [Abstract] [Full Text] [PDF]
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K. J. Suter, C. R. Pohl, and M. E. Wilson Circulating Concentrations of Nocturnal Leptin, Growth Hormone, and Insulin-Like Growth Factor-I Increase before the Onset of Puberty in Agonadal Male Monkeys: Potential Signals for the Initiation of Puberty J. Clin. Endocrinol. Metab., February 1, 2000; 85(2): 808 - 814. [Abstract] [Full Text]
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L. K. Hilton and A. B. Loucks Low energy availability, not exercise stress, suppresses the diurnal rhythm of leptin in healthy young women Am J Physiol Endocrinol Metab, January 1, 2000; 278(1): E43 - E49. [Abstract] [Full Text] [PDF]
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J. G. Hohmann, T. H. Teal, D. K. Clifton, J. Davis, V. J. Hruby, G. Han, and R. A. Steiner Differential role of melanocortins in mediating leptin's central effects on feeding and reproduction Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2000; 278(1): R50 - R59. [Abstract] [Full Text] [PDF]
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R. S. Ahima, J. Kelly, J. K. Elmquist, and J. S. Flier Distinct Physiologic and Neuronal Responses to Decreased Leptin and Mild Hyperleptinemia Endocrinology, November 1, 1999; 140(11): 4923 - 4931. [Abstract] [Full Text]
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M. Caprio, A. M. Isidori, A. R. Carta, C. Moretti, M. L. Dufau, and A. Fabbri Expression of Functional Leptin Receptors in Rodent Leydig Cells Endocrinology, November 1, 1999; 140(11): 4939 - 4947. [Abstract] [Full Text]
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T. Sir-Petermann, M. Maliqueo, A. Palomino, D. Vantman, S.E. Recabarren, and L. Wildt Episodic leptin release is independent of luteinizing hormone secretion Hum. Reprod., November 1, 1999; 14(11): 2695 - 2699. [Abstract] [Full Text] [PDF]
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M. P. Warren, F. Voussoughian, E. B. Geer, E. P. Hyle, C. L. Adberg, and R. H. Ramos Functional Hypothalamic Amenorrhea: Hypoleptinemia and Disordered Eating J. Clin. Endocrinol. Metab., March 1, 1999; 84(3): 873 - 877. [Abstract] [Full Text]
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M. J. Cunningham, D. K. Clifton, and R. A. Steiner Leptin's Actions on the Reproductive Axis: Perspectives and Mechanisms Biol Reprod, February 1, 1999; 60(2): 216 - 222. [Abstract] [Full Text] [PDF]
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 M. E. Majdoubi, A. Sahu, S. Ramaswamy, and T. M. Plant Neuropeptide Y: A hypothalamic brake restraining the onset of puberty in primates PNAS, May 23, 2000; 97(11): 6179 - 6184. [Abstract] [Full Text] [PDF]
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