THE STIMULATION OF RAT LEYDIG-CELL STEROIDOGENESIS BY HUMAN OVARIAN STEROIDOGENESIS-INDUCING PROTEIN (SIP) MAY NOT REQUIRE ENDOGENOUS CAMP

Recently a protein from ovarian follicular fluid was isolated which st imulates steroid production in different cells (Khan et al., 1990). Th e present study was performed to further characterize the short term e ffects of this steroidogensis-inducing protein (SIP) on steroid produc tion in isolated rat Leydig cells and to compare the effects with LH/h CG and LHRH. SIP stimulated testosterone production in a dose-dependen t manner. In Leydig cells isolated from adult rats the degree of stimu lation was much higher than that obtained with hCG, dibutyril cAMP (db cAMP) or LHRH. Moreover, the stimulated steroid production in the pre sence of hCG or db cAMP was further enhanced by SIP. The time courses of hCG and SIP action on testosterone production were comparable and m aximal stimulation of steroid production was obtained within one hour. In contrast to hCG, SIP did not stimulate cAMP production. An antagon ist of LHRH action was unable to block the effects of SIP on Leydig ce lls indicating that SIP does not act via LHRH receptors. Neither SIP n or LH could further stimulate the steroid production in the presence o f 22-R-OH-cholesterol, illustrating that both stimulators control the availability of cholesterol as substrate. An inhibitor of mitochondria l cholesterol side chain cleavage (CSCC), aminoglutethemide, completel y blocked the stimulatory effects of SIP and LH/hCG. Thus the effects of SIP on steroid production are not the result of conversion of conta minating steroids in the SIP-preparation. SIP and LH/hCG actions were also blocked when the cells were incubated in the presence of cyclohex imide. The data indicate that SIP may stimulate steroidogenesis at the level of CSCC-activity via pathways which require protein synthesis a nd which may be independent of cAMP.