INHIBITION OF THE LUTEINIZING HORMONE-DEPENDENT INDUCTION OF CHOLESTEROL SIDE-CHAIN CLEAVAGE ENZYME IN IMMATURE RAT LEYDIG-CELLS BY SERTOLI-CELL PRODUCTS

The modulation of the luteinizing hormone (LH) induction of cholestero l side chain cleavage (CSCC) enzyme in immature rat Leydig cells was s tudied using rat Sertoli cell-conditioned medium (SCCM), which stimula tes short-term endogenous steroid production. Luteinizing hormone incr eased the CSCC enzyme activity 10-fold in cells cultured for 7 days in the absence of hormones. This enzyme induction was abolished almost c ompletely in the presence of SCCM. The inhibition was dose dependent ( half-maximal effect at 5 mg protein/l) and paralleled by a decrease in the amount of cytochrome P-450(scc) (P-450(scc)) enzyme. There were n o indications for loss of cell viability. The inhibitory action of SCC M could be localized at the level of adenylate cyclase activation and at steps beyond cyclic adenosine monophosphate production. The inhibit ion was not specific far Sertoli cell products because conditioned med ia from different cell Lines and media from isolated rat hepatocytes d isplayed similar effects. Trypsin treatment of SCCM destroyed the acti vity whereas the bioactivity could resist heating for 5 min at 100 deg rees C. Generally occurring (growth) factors, such as epidermal growth factor or tumor necrosis factor cu, may have contributed to the obser ved inhibitory effects of SCCM. These inhibitory effects of Sertoli ce ll products in vitro are in contrast to stimulatory effects of Sertoli cells on Leydig cell steroidogenesis in vivo after FSK administration .