The in vivo and in vitro effects of exogenous leptin on ovulation in the rat

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 l eptin protein has been localized in many reproductive tissues, including th e 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 o n ovulation in the rat ovary, both in vivo and in vitro, was investigated. Ip administration of leptin (30 mu g at 3 hourly intervals for 15 h) to imm ature 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 l eptin-treated animals (P < 0.001). Plasma progesterone and estradiol levels were analyzed immediately before ovulation, and neither was altered signif icantly in animals receiving the leptin treatment. Food consumption and bod y weight decreased following leptin treatment; however, a loss in body weig ht alone (pair-fed controls) was insufficient to explain the decrease in ov ulation observed in the leptin-treated animals. in vitro perfusion of FSH-p rimed whole ovaries showed that treatment with leptin in combination with L H significantly decreased ovulations from 5.7 +/- 1.6 per ovary perfused wi th LH alone to 1.3 +/- 0.6 in those with LH and 1 mu g/ml leptin (P < 0.05) . Progesterone and estradiol levels in the samples taken during the perfusi on period were unaffected by leptin treatment. In summary, leptin administr ation 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.