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 cholesterol side chain cleavage (CSCC) enzyme in immature rat Leydig cells was studied using rat Sertoli cell-conditioned medium (SCCM), which stimulates short-term endogenous steroid production. Luteinizing hormone increased the CSCC enzyme activity 10-fold in cells cultured for 7 days in the absence of hormones. This enzyme induction was abolished almost completely 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-450scc (P-450scc) enzyme. There were no indications for loss of cell viability. The inhibitory action of SCCM could be localized at the level of adenylate cyclase activation and at steps beyond cyclic adenosine monophosphate production. The inhibition was not specific for Sertoli cell products because conditioned media from different cell lines and media from isolated rat hepatocytes displayed similar effects. Trypsin treatment of SCCM destroyed the activity whereas the bioactivity could resist heating for 5 min at 100 degrees C. Generally occurring (growth) factors, such as epidermal growth factor or tumor necrosis factor alpha, may have contributed to the observed inhibitory effects of SCCM. These inhibitory effects of Sertoli cell products in vitro are in contrast to stimulatory effects of Sertoli cells on Leydig cell steroidogenesis in vivo after FSH administration.
van Haren
L
L
Department of Endocrinology & Reproduction, Erasmus University Rotterdam, The Netherlands.
Flinterman
J F
JF
Rommerts
F F
FF
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D017077:Culture Media, Conditioned; D004789:Enzyme Activation; D004790:Enzyme Induction / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006358:Hot Temperature; D007985:Leydig Cells / Q000201:enzymology*; D007986:Luteinizing Hormone / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012708:Sertoli Cells / Q000378:metabolism*; D015398:Signal Transduction; D014357:Trypsin / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D017077:Culture Media, Conditioned; D014409:Tumor Necrosis Factor-alpha; D004815:Epidermal Growth Factor; D007986:Luteinizing Hormone; D002786:Cholesterol Side-Chain Cleavage Enzyme; D014357:Trypsin; D000262:Adenylyl Cyclases