Interleukin-6 inhibits the expression of luteinizing hormone receptor mRNAduring the maturation of cultured rat granulosa cells

Interleukin-6 (IL-6) and its receptor components have been shown to be pres ent in rat follicular granulosa cells. The present study was designed to ex amine the effect of this cytokine on changes in expression of the luteinizi ng hormone receptor (LHR) messenger RNA and of the steroidogenic enzyme, CY P11A1 (cytochrome P450 sec) in an in vitro model of granulosa cell maturati on. Ovarian granulosa cells harvested from immature rats 2 days after treat ment with equine chorionic gonadotropin were cultured for 48 h in media con taining 10% fetal bovine serum. They were then transferred to a chemically defined serum-free medium and cultured for an additional 72 h. Within 24 h of transfer, the expressions of LHR and CYP11A1 mRNA increased significantl y and remained increased for 72 h. The cells responded to exposure to FSH, but not LH, by an increase in production of cAMP before the additional 72 h of culture. The cAMP response to LH was attained within 24 h and persisted for 72 h, whereas the response to FSH decreased continuously with time. In clusion of IL-6 in the culture medium caused a dose-dependent decrease in e xpression of LHR mRNA, in addition to a decrease in the cAMP response to LH . Immunoneutralization oi endogenous granulosa cell IL-6 resulted in an inc rease in expression of LHR mRNA, but not CYP11A1 mRNA. The results are cons istent with the view that IL-6 may have a physiological role in the maturat ion of ovarian follicles by modulating the attainment of the LHR in granulo sa cells.