The stimulation of rat Leydig cell steroidogenesis by human ovarian steroidogenesis-inducing protein (SIP) may not...

Recently a protein from ovarian follicular fluid was isolated which stimulates steroid production in different cells (Khan et al., 1990). The present study was performed to further characterize the short term effects of this steroidogensis-inducing protein (SIP) on steroid production in isolated rat Leydig cells and to compare the effects with LH/hCG and LHRH. SIP stimulated testosterone production in a dose-dependent manner. In Leydig cells isolated from adult rats the degree of stimulation was much higher than that obtained with hCG, dibutyryl cAMP (db cAMP) or LHRH. Moreover, the stimulated steroid production in the presence of hCG or db cAMP was further enhanced by SIP. The time courses of hCG and SIP action on testosterone production were comparable and maximal stimulation of steroid production was obtained within one hour. In contrast to hCG, SIP did not stimulate cAMP production. An antagonist of LHRH action was unable to block the effects of SIP on Leydig cells indicating that SIP does not act via LHRH receptors. Neither SIP nor LH could further stimulate the steroid production in the presence of 22-R-OH-cholesterol, illustrating that both stimulators control the availability of cholesterol as substrate. An inhibitor of mitochondrial cholesterol side chain cleavage (CSCC), aminoglutethemide, completely blocked the stimulatory effects of SIP and LH/hCG. Thus the effects of SIP on steroid production are not the result of conversion of contaminating steroids in the SIP-preparation. SIP and LH/hCG actions were also blocked when the cells were incubated in the presence of cycloheximide.(ABSTRACT TRUNCATED AT 250 WORDS)