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The in Vivo and in Vitro Effects of Exogenous Leptin on Ovulation in the Rat¹

Reproductive Medicine Unit (P.S.D., K.H.V.d.H., C.R.M., N.K.R., D.T.A., R.J.N.), Department of Obstetrics & Gynecology, The University of Adelaide, The Queen Elizabeth Hospital, Woodville 5011, S.A. Australia; and Department of Obstetrics and Gynecology (D.A.M.), Cedars-Sinai Burns & Allen Research Institute, Los Angeles, California 90048

Address all correspondence and requests for reprints to: Robert J. Norman, M.D., University of Adelaide, Queen Elizabeth Hospital, Department of Obstetrics/Gynecology, Woodville 5011, S.A. Australia. E-mail: robert.norman{at}adelaide.edu.au

Leptin, a hormonal product of the Lep gene, is expressed by adipocytes and is thought to play a role in regulating food intake and reproduction. The leptin protein has been localized in many reproductive tissues, including the ovary. Several publications indicate that the ovary is directly affected by leptin and that leptin may be a factor linking obesity and reproductive dysfunction. In this study, the effect of systemic leptin administration on ovulation in the rat ovary, both in vivo and in vitro, was investigated. Ip administration of leptin (30 µg at 3 hourly intervals for 15 h) to immature gonadotropin-primed rats caused a decline in ovulation in vivo, from 15.9 ± 2.0 oocytes in the control animals to 5.3 ± 1.6 oocytes in the leptin-treated animals (P < 0.001). Plasma progesterone and estradiol levels were analyzed immediately before ovulation, and neither was altered significantly in animals receiving the leptin treatment. Food consumption and body weight decreased following leptin treatment; however, a loss in body weight alone (pair-fed controls) was insufficient to explain the decrease in ovulation observed in the leptin-treated animals. In vitro perfusion of FSH-primed whole ovaries showed that treatment with leptin in combination with LH significantly decreased ovulations from 5.7 ± 1.6 per ovary perfused with LH alone to 1.3 ± 0.6 in those with LH and 1 µg/ml leptin (P < 0.05). Progesterone and estradiol levels in the samples taken during the perfusion period were unaffected by leptin treatment. In summary, leptin administration resulted in fewer ovulations, both in vivo and in vitro, but did not influence steroid levels. Systemic leptin administration at these doses can therefore inhibit ovulation, a process that occurs through a direct effect on the ovary.

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