Inhibitory action of leptin on early follicular growth differs in immatureand adult female mice

In order to investigate the action of leptin on early follicular growth, pr eantral follicles, 95-215 pm in diameter were mechanically isolated from th e ovaries of BDF1 hybrid immature (11-day-old) and adult (8-wk-old) mice, a nd cultured for 4 days in: vitro. Follicular growth was assessed by daily c hanges in folicular diameter and by the amount of estradiol and immunoreact ive (IR)-inhibin released into the culture medium at Day 4. Preantral folli cles from immature mice showed a significant development in follicular grow th as a result of stimulation by GH (1 mIU/ml), insulin-like growth factor (IGF)-I (100 ng/ml) + FSH (100 mIU/ml), and CH (1 mIU/ml) + FSH (100 mIU/ml ), Although leptin at concentrations of 1-1000 ng/ml did not have any signi ficant effect on follicular growth stimulated by IGF-I or GH, if significan tly inhibited follicular growth in a dose-related manner when follicles wer e stimulated by ICF-I + FSH and GH c FSH, respectively, suggesting that lep tin attenuated the additive effect of FSH. On the other hand, preantral fol licles from adult mice were cultured in the presence of FSH, and FSH-depend ent follicular growth was inhibited by leptin in a dose-related manner, Bec ause FSH stimulates cAMP production, we investigated the involvement of cAM P in the inhibitory mechanisms of leptin. Preantral follicles from immature and adult mice were cultured in the presence of either 8-Br-cAMP or forsko lin. Both 8-Br-cAMP and forskolin significantly increased follicular diamet er and hormone secretion in both immature and adult mice. However, 8-Br-cAM P and forskolin-stimulated follicle growth and hormone secretion were signi ficantly inhibited in immature mice by coadministration of leptin, whereas growth of preantral follicles from adult mice was not inhibited by addition of leptin to cultures. These results indicate that leptin causes an inhibi tory effect on the early follicular development of both immature and adult mice, but the inhibitory mechanisms of leptin are different.