Endocrinology, Vol 137, 3144-3147, Copyright © 1996 by Endocrine Society

ARTICLES

Leptin is a metabolic signal to the reproductive system

IA Barash, CC Cheung, DS Weigle, H Ren, EB Kabigting, JL Kuijper, DK Clifton and RA Steiner
Department of obstetrics & Gynecology, University of Washington, Seatle, WA 98195-6460.

Leptin, a newly-discovered hormonal product of the obese (ob) gene, is expressed by adipocytes and thought to play a role in the regulation of food intake and metabolism. We tested the hypothesis that leptin signals metabolic information to the reproductive system by examining its effects on the reproductive system of ob/ob mice, which have a congenital deficiency in leptin and are infertile. We treated pair-fed males and females with leptin (50 microg twice daily, ip) or vehicle (n=10/group) for 14 days, after which the animals were bled and killed. Leptin-treated females had significantly elevated serum levels of LH, increased ovarian and uterine weights, and stimulated aspects of ovarian and uterine histology compared to controls. Leptin-treated males had significantly elevated serum levels of FSH, increased testicular and seminal vesicle weights, greater seminal vesicle epithelial cell height, and elevated sperm counts compared to controls. These results demonstrate that leptin stimulates the reproductive endocrine system in both sexes of ob/ob mice and suggest that leptin may serve as a permissive signal to the reproductive system of normal animals.

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				S. M. Hileman, D. D. Pierroz, and J. S. Flier Leptin, Nutrition, and Reproduction: Timing Is Everything J. Clin. Endocrinol. Metab., February 1, 2000; 85(2): 804 - 807. [Full Text]

				J. E. Schneider, R. M. Blum, and G. N. Wade Metabolic control of food intake and estrous cycles in Syrian hamsters. I. Plasma insulin and leptin Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2000; 278(2): R476 - R485. [Abstract] [Full Text] [PDF]

				D. R. Mann, M. A. Akinbami, K. G. Gould, and V. D. Castracane A Longitudinal Study of Leptin During Development in the Male Rhesus Monkey: The Effect of Body Composition and Season on Circulating Leptin Levels Biol Reprod, February 1, 2000; 62(2): 285 - 291. [Abstract] [Full Text]

				P. Niewiarowski, M. Balk, and R. Londraville Phenotypic effects of leptin in an ectotherm: a new tool to study the evolution of life histories and endothermy? J. Exp. Biol., January 1, 2000; 203(2): 295 - 300. [Abstract] [PDF]

				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]

				A. Walczewska, W. H. Yu, S. Karanth, and S. M. McCann Estrogen and Leptin Have Differential Effects on FSH and LH Release in Female Rats Experimental Biology and Medicine, November 1, 1999; 222(2): 170 - 177. [Abstract] [Full Text]

				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]

				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]

				A. M. Isidori, M. Caprio, F. Strollo, C. Moretti, G. Frajese, A. Isidori, and A. Fabbri Leptin and Androgens in Male Obesity: Evidence for Leptin Contribution to Reduced Androgen Levels J. Clin. Endocrinol. Metab., October 1, 1999; 84(10): 3673 - 3680. [Abstract] [Full Text] [PDF]

				M. Ozata, I. C. Ozdemir, and J. Licinio Human Leptin Deficiency Caused by a Missense Mutation: Multiple Endocrine Defects, Decreased Sympathetic Tone, and Immune System Dysfunction Indicate New Targets for Leptin Action, Greater Central than Peripheral Resistance to the Effects of Leptin, and Spontaneous Correction of Leptin-Mediated Defects J. Clin. Endocrinol. Metab., October 1, 1999; 84(10): 3686 - 3695. [Abstract] [Full Text] [PDF]

				J. E. Schneider and D. Zhou Interactive effects of central leptin and peripheral fuel oxidation on estrous cyclicity Am J Physiol Regulatory Integrative Comp Physiol, October 1, 1999; 277(4): R1020 - R1024. [Abstract] [Full Text] [PDF]

				I. S. Farooqi, S. A. Jebb, G. Langmack, E. Lawrence, C. H. Cheetham, A. M. Prentice, I. A. Hughes, M. A. McCamish, and S. O'Rahilly Effects of Recombinant Leptin Therapy in a Child with Congenital Leptin Deficiency N. Engl. J. Med., September 16, 1999; 341(12): 879 - 884. [Full Text] [PDF]

				T. L. Bützow, J. M. Moilanen, M. Lehtovirta, T. Tuomi, O. Hovatta, R. Siegberg, C.-G. Nilsson, and D. Apter Serum and Follicular Fluid Leptin during in Vitro Fertilization: Relationship among Leptin Increase, Body Fat Mass, and Reduced Ovarian Response J. Clin. Endocrinol. Metab., September 1, 1999; 84(9): 3135 - 3139. [Abstract] [Full Text]

				L. Poretsky, N. A. Cataldo, Z. Rosenwaks, and L. C. Giudice The Insulin-Related Ovarian Regulatory System in Health and Disease Endocr. Rev., August 1, 1999; 20(4): 535 - 582. [Abstract] [Full Text] [PDF]

				L. Jin, B. G. Burguera, M. E. Couce, B. W. Scheithauer, J. Lamsan, N. L. Eberhardt, E. Kulig, and R. V. Lloyd Leptin and Leptin Receptor Expression in Normal and Neoplastic Human Pituitary: Evidence of a Regulatory Role for Leptin on Pituitary Cell Proliferation J. Clin. Endocrinol. Metab., August 1, 1999; 84(8): 2903 - 2911. [Abstract] [Full Text]

				J. Kitawaki, I. Kusuki, H. Koshiba, K. Tsukamoto, and H. Honjo Leptin directly stimulates aromatase activity in human luteinized granulosa cells Mol. Hum. Reprod., August 1, 1999; 5(8): 708 - 713. [Abstract] [Full Text] [PDF]

				A. Cai and J. F. Hyde The Human Growth Hormone-Releasing Hormone Transgenic Mouse as a Model of Modest Obesity: Differential Changes in Leptin Receptor (OBR) Gene Expression in the Anterior Pituitary and Hypothalamus after Fasting and OBR Localization in Somatotrophs Endocrinology, August 1, 1999; 140(8): 3609 - 3614. [Abstract] [Full Text]

				M. C. Henson, V. D. Castracane, J. S. O’Neil, T. Gimpel, K. F. Swan, A. E. Green, and W. Shi Serum Leptin Concentrations and Expression of Leptin Transcripts in Placental Trophoblast with Advancing Baboon Pregnancy J. Clin. Endocrinol. Metab., July 1, 1999; 84(7): 2543 - 2549. [Abstract] [Full Text]