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Original Studies |
Research Centre for Endocrinology and Metabolism, Departments of Internal Medicine (C.K., K.L., L.M.S.C., B.C.) and Department of Obstetrics and Gynecology (E.S., C.B., H.B.), Sahlgrenska University Hospital; and the Department of Physiology and Pharmacology (E.S., H.B.), Goteborg University, Goteborg; and the Department of Molecular Biology, Pharmacia and Upjohn (P.L.), Stockholm, Sweden
Address all correspondence and requests for reprints to: Dr. Björn Carlsson, Research Center for Endocrinology and Metabolism, Department of Internal Medicine, Gröna Stråket 8, Sahlgrenska University Hospital, S-413 45 Goteborg, Sweden. E-mail: bjorn.carlsson{at}ss.gu.se
The size of body fat stores is known to influence fertility, indicating a link between adipose tissue and the reproductive system. Studies in mice have identified the adipocyte-derived hormone, leptin (Ob protein), as a possible mediator of this effect. The aim of this study was to investigate the possibility that leptin may have direct effects on the human ovary. To probe this hypothesis we first analyzed the expression of leptin receptors in the human ovary. Transcripts encoding both the long and short isoforms of the leptin receptor were present in human granulosa cells and thecal cells; however, the short isoforms were expressed at much higher levels. Immunoreactive leptin was present in follicular fluid at levels similar to those found in serum. ob gene expression, however, was undetectable in the ovary, as determined by reverse transcription-PCR, whereas it was easily detected in adipose tissue. To determine whether leptin could induce a biological response in ovarian cells, we examined the effect of leptin on estradiol production in cultured granulosa cells. Leptin (100 ng/mL) inhibited LH (0.1 ng/mL)-stimulated estradiol production. In contrast, leptin had no effect on estradiol production in the absence of LH.
In conclusion, this study has demonstrated that the leptin receptor is expressed in the human ovary, that leptin is present in follicular fluid, and that leptin can induce a biological response in ovarian cells. These results suggest that leptin may have a direct effect on the human ovary.
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J. Kitawaki, H. Koshiba, H. Ishihara, I. Kusuki, K. Tsukamoto, and H. Honjo Expression of Leptin Receptor in Human Endometrium and Fluctuation during the Menstrual Cycle J. Clin. Endocrinol. Metab., May 1, 2000; 85(5): 1946 - 1950. [Abstract] [Full Text] |
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A. E. Green, J. S. O'neil, K. F. Swan, R. P. Bohm Jr., M. S. Ratterree, and M. C. Henson Leptin Receptor Transcripts Are Constitutively Expressed in Placenta and Adipose Tissue with Advancing Baboon Pregnancy Experimental Biology and Medicine, April 1, 2000; 223(4): 362 - 366. [Abstract] [Full Text] [PDF] |
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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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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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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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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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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] |
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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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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] |
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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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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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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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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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A. Glasow, A. Haidan, U. Hilbers, M. Breidert, J. Gillespie, W. A. Scherbaum, G. P. Chrousos, and S. R. Bornstein Expression of Ob Receptor in Normal Human Adrenals: Differential Regulation of Adrenocortical and Adrenomedullary Function by Leptin J. Clin. Endocrinol. Metab., December 1, 1998; 83(12): 4459 - 4466. [Abstract] [Full Text] |
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P. D. Finn, M. J. Cunningham, K.-Y. F. Pau, H. G. Spies, D. K. Clifton, and R. A. Steiner The Stimulatory Effect of Leptin on the Neuroendocrine Reproductive Axis of the Monkey Endocrinology, November 1, 1998; 139(11): 4652 - 4662. [Abstract] [Full Text] [PDF] |
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