Rabbit ovarian production of interleukin-6 and its potential effects on gonadotropin-induced progesterone secretion in granulosa and theca cells

Recent studies suggest that non-steroid factors, such as cytokines, may pla y a role in ovarian processes. The purpose of this study was to explore cel lular sites of interleukin (IL)-6 biosynthesis in rabbit follicles and to i nvestigate IL-6 modulation in granulosa and theca cell functions. In this r eport development of rabbit preovulatory follicles was induced by 200 mIU e quine chorionic gonadotropin (eCG) daily for 2 days. Seventy-two hours afte r the last injection ovaries were excised and granulosa and theca cells iso lated. The two types of cells were preincubated for 24 h in Minimum Essenti al Medium (MEM) with 5% fetal calf serum (FCS), and then incubated for 24 h in MEM-2.5% FCS with appropriate stimulants. Results showed that rabbit gr anulosa and theca cell culture supernatants contained IL-6 bioactivity and that its production was inhibited by FSH and human CG and stimulated by IL- 1. IL-6 inhibited gonadotropin-induced progesterone production, but not bas al secretion, in both cell types, without a cytotoxic effect. IL-6 affected cAMP generation and steps distal to cAMP formation, but the mechanism of I L-6 action on progesterone differed in granulosa and theca cells. Taken tog ether our results suggest that gonadotropins, by inhibiting IL-6 production , could control, in our model, IL-6 modulation of gonadotropin action on st eroidogenesis.