Leptin antagonizes the insulin-like growth factor-I augmentation of steroidogenesis in granulosa and theca cells of the human ovary

There is increasing evidence that leptin is a physiological link between ob esity and infertility. Although leptin receptors have been demonstrated in human ovaries, there is no information regarding the effects of leptin on c ells from developing ovarian follicles. To test the direct effects of lepti n on human ovarian cells, granulosa cells (GC) and theca cells were isolate d from the ovaries of regularly cycling women. Serum was obtained at the ti me of surgery, and follicular fluid was aspirated from the follicles before isolation of the ovarian cells. Leptin concentrations were similar in foll icular fluid and serum. RT-PCR analysis demonstrated that the long, signali ng form of the leptin receptor was expressed in both theca and GC. In cultu red GC, leptin had no effect on estradiol production, alone or in the prese nce of FSH, but caused a concentration-related inhibition of the insulin-li ke growth factor I (IGF-I) augmentation of FSH-stimulated estradiol product ion. The effect ofleptin was specific, because there was no effect on proge sterone production. In cultured theca cells, leptin did not alter androsten edione production, alone or in the presence of LH. Leptin caused a concentr ation-related inhibition of the IGF-I augmentation of LH-stimulated androst enedione production. These data demonstrate that leptin can directly inhibi t IGF-I action in ovarian theca and GC at concentrations commonly present i n obese women.