Regulation of testicular P-450 cholesterol side-chain cleavage and P-450 C17-20 lyase/C17 hydroxylase enzymes in the neonatal and adult rat.
Adult Leydig cells respond to LH or hCG with an initial stimulation of testosterone secretion followed by LH receptor down-regulation and blockade of androgen biosynthesis. In contrast, fetal Leydig cells respond with increased LH receptor number and enhanced steroidogenesis. In this study, the molecular mechanisms of high-dose hCG treatment on steroidogenesis in adult and neonatal testes (containing predominantly the fetal generation of Leydig cells) were examined using two recombinant DNA clones specific for enzymes of the rat steroidogenic pathway (P-450 cholesterol side-chain cleavage enzyme, P-450scc and P-450 17 alpha-hydroxylase/C17-20 lyase, P-450c17). We treated adult (60 days of age) and neonatal (2 days of age) rats with a single high dose of hCG (600 IU/kg), sc. The high dose of hCG caused neonatal testicular P450scc and P450c17 mRNA levels to increase, and stimulated adult testicular P450scc mRNA levels, but caused a decrease in adult P450c17 mRNA levels. These studies suggest that high doses of hCG regulate testosterone production differently in adult and fetal Leydig cells at a pretranslational level of the P450c17 enzyme, while mRNA for P450scc is stimulated in both the adult and fetal Leydig cell.
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Department of Physiology and Biophysics, University of Southern California, School of Medicine, Los Angeles.
McDonough
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A
Farley
R A
RA
Warren
D W
DW
D000375:Aging / Q000378:metabolism*; D000446:Aldehyde-Lyases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D000728:Androgens / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D007985:Leydig Cells / Q000201:enzymology / Q000648:ultrastructure; D007986:Luteinizing Hormone / Q000494:pharmacology; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D013737:Testis / Q000166:cytology / Q000201:enzymology*; D013739:Testosterone / Q000378:metabolism
D000728:Androgens; D006063:Chorionic Gonadotropin; D012333:RNA, Messenger; D013739:Testosterone; D007986:Luteinizing Hormone; D003577:Cytochrome P-450 Enzyme System; D013254:Steroid 17-alpha-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme; D000446:Aldehyde-Lyases