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Department of Animal Science, Oklahoma State University, Stillwater, Oklahoma 74078-0425
Address all correspondence and reprint requests to: Leon J. Spicer, Ph.D., Department of Animal Science, Oklahoma State University, 114 Animal Science Building, Stillwater, Oklahoma 74078-0425.
Leptin, a recently-discovered hormonal product of the obese gene,
circulates in the blood at levels paralleling those of fat reserves and
regulates satiety and improves reproductive performance if injected
into mice lacking circulating leptin. Therefore, we tested the
hypothesis that leptin signals metabolic information to the
reproductive system by directly affecting granulosa cell function.
Doses of 10–300 ng/ml leptin had no effect (P >
0.10) on basal or insulin-induced numbers of granulosa cells cultured
from small (1–5 mm) or large (
8 mm) bovine follicles. Similarly, 30
and 300 ng/ml leptin had no effect (P > 0.10) on
basal estradiol production. However, leptin, in a dose-dependent
manner, inhibited (P < 0.05) insulin-induced
progesterone and estradiol production by granulosa cells from small and
large follicles. Leptin did not compete for specific
125I-insulin binding to granulosa cells. Furthermore,
specific binding of 125I-leptin was demonstrable in
granulosa cells. In conclusion, leptin, at physiological levels, can
directly attenuate insulin-induced steroidogenesis of granulosa cells
without affecting proliferation of this ovarian cell type. These
results provide evidence to support the hypothesis that leptin can act
as a metabolic signal to the reproductive system via direct action at
the ovarian level.
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P. S. Duggal, K. H. Van der Hoek, C. R. Milner, N. K. Ryan, D. T. Armstrong, D. A. Magoffin, and R. J. Norman The in Vivo and in Vitro Effects of Exogenous Leptin on Ovulation in the Rat Endocrinology, June 1, 2000; 141(6): 1971 - 1976. [Abstract] [Full Text] [PDF]
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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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 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]
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R. J. Zachow, S. R. Weitsman, and D. A. Magoffin Leptin Impairs the Synergistic Stimulation by Transforming Growth Factor-{beta} of Follicle-Stimulating Hormone-Dependent Aromatase Activity and Messenger Ribonucleic Acid Expression in Rat Ovarian Granulosa Cells Biol Reprod, October 1, 1999; 61(4): 1104 - 1109. [Abstract] [Full Text]
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 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]
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 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]
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M. Rosenbaum and R. L. Leibel Role of Gonadal Steroids in the Sexual Dimorphisms in Body Composition and Circulating Concentrations of Leptin J. Clin. Endocrinol. Metab., June 1, 1999; 84(6): 1784 - 1789. [Full Text]
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T. Sir-Petermann, V. Piwonka, F. Perez, M. Maliqueo, S.E. Recabarren, and L. Wildt Are circulating leptin and luteinizing hormone synchronized in patients with polycystic ovary syndrome? Hum. Reprod., June 1, 1999; 14(6): 1435 - 1439. [Abstract] [Full Text] [PDF]
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J. D. Brannian, Y. Zhao, and M. McElroy Leptin inhibits gonadotrophin-stimulated granulosa cell progesterone production by antagonizing insulin action Hum. Reprod., June 1, 1999; 14(6): 1445 - 1448. [Abstract] [Full Text] [PDF]
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 M. A. Pelleymounter, M. B. Baker, and M. McCaleb Does estradiol mediate leptin's effects on adiposity and body weight? Am J Physiol Endocrinol Metab, May 1, 1999; 276(5): E955 - E963. [Abstract] [Full Text] [PDF]
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 C. S. Mantzoros The Role of Leptin in Human Obesity and Disease: A Review of Current Evidence Ann Intern Med, April 20, 1999; 130(8): 671 - 680. [Abstract] [Full Text] [PDF]
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D. Barkan, H. Jia, A. Dantes, L. Vardimon, A. Amsterdam, and M. Rubinstein Leptin Modulates the Glucocorticoid-Induced Ovarian Steroidogenesis Endocrinology, April 1, 1999; 140(4): 1731 - 1738. [Abstract] [Full Text]
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I.E. Messinis, S.D. Milingos, E. Alexandris, I. Kariotis, G. Kollios, and K. Seferiadis Leptin concentrations in normal women following bilateral ovariectomy Hum. Reprod., April 1, 1999; 14(4): 913 - 918. [Abstract] [Full Text] [PDF]
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S. K. Agarwal, K. Vogel, S. R. Weitsman, and D. A. Magoffin Leptin Antagonizes the Insulin-Like Growth Factor-I Augmentation of Steroidogenesis in Granulosa and Theca Cells of the Human Ovary J. Clin. Endocrinol. Metab., March 1, 1999; 84(3): 1072 - 1076. [Abstract] [Full Text]
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B. A. Henry, J. W. Goding, W. S. Alexander, A. J. Tilbrook, B. J. Canny, F. Dunshea, A. Rao, A. Mansell, and I. J. Clarke 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 Function Endocrinology, March 1, 1999; 140(3): 1175 - 1182. [Abstract] [Full Text]
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K. O. Klein, K. A. Larmore, E. de Lancey, J. M. Brown, R. V. Considine, and S. G. Hassink Effect of Obesity on Estradiol Level, and Its Relationship to Leptin, Bone Maturation, and Bone Mineral Density in Children J. Clin. Endocrinol. Metab., October 1, 1998; 83(10): 3469 - 3475. [Abstract] [Full Text]
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F. P. Pralong, R. Roduit, G. Waeber, E. Castillo, F. Mosimann, B. Thorens, and R. C. Gaillard Leptin Inhibits Directly Glucocorticoid Secretion by Normal Human and Rat Adrenal Gland Endocrinology, October 1, 1998; 139(10): 4264 - 4268. [Abstract] [Full Text] [PDF]
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