EXPRESSION OF FUNCTIONAL LEPTIN RECEPTORS IN THE HUMAN OVARY

The size of body fat stores is known to influence fertility, indicatin g a link between adipose tissue and the reproductive system. Studies i n mice have identified the adipocyte-derived hormone, leptin (Ob prote in), 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 expres sion of leptin receptors in the human ovary. Transcripts encoding both the long and short isoforms of the leptin receptor were present in hu man 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 e xpression, however, was undetectable in the ovary, as determined by re verse transcription-PCR, whereas it was easily detected in adipose tis sue. To determine whether leptin could induce a biological response in ovarian cells, we examined the effect of leptin on estradiol producti on in cultured granulosa cells. Leptin (100 ng/mL) inhibited LH (0.1 n g/ml)-stimulated estradiol production. In contrast, leptin had no effe ct on estradiol production in the absence of LH. In conclusion, this s tudy has demonstrated that the leptin receptor is expressed in the hum an ovary, that leptin is present in follicular fluid, and that leptin can induce a biological response in ovarian cells. These results sugge st that leptin may have a direct effect on the human ovary.