INHIBITION BY GONADOTROPINS OF INTERLEUKIN-1 PRODUCTION BY RABBIT GRANULOSA AND THECA CELLS - EFFECTS ON GONADOTROPIN-INDUCED PROGESTERONE PRODUCTION

Increasing evidence suggests that cytokines may play a role in ovarian processes. The purpose of this study was to determine if interleukin- 1 (IL-1) could modulate rabbit pre-ovulatory follicular function and t o explore cellular sites of IL-1 biosynthesis in rabbit follicles. Dev elopment of rabbit pre-ovulatory follicles was induced by 200 mIU equi ne chorionic gonadotropin daily for 2 days. Seventy-two hours after th e last injection, ovaries were excised and granulosa and theca cells i solated. The two types of cell were pre-incubated for 24 h in Minimum Essential Medium (MEM) with 5% fetal calf serum (FCS), and then incuba ted for 24 h in MEM with 2.5% FCS with appropriate stimulants. Results showed that rabbit granulosa and theca cell culture supernatants cont ain IL-1 bioactivity and that this bioactivity was diminished by gonad otropins, FSH and human chorionic gonadotropin, in a dose-dependent ma nner. Low doses of IL-1 (1 ng/ml) inhibited gonadotropin-induced proge sterone production in both cell types and at the same time increased c ell numbers. A study of the mechanism of IL-1 action demonstrated that it affects cAMP generation, and also steps distal to cAMP formation. We conclude that in our model gonadotropins, by inhibiting IL-1 produc tion, could control IL-1 modulation of gonadotropin action on steroido genesis.