[Inhibition of steroidogenesis by ketoconazole. Therapeutic uses].
Ketoconazole, a broad-spectrum imidazole antimycotic agent, interferes with cytochrome P-450 enzyme systems in several organs (testis, ovary, adrenal gland, kidney, liver). It inhibits cholesterol synthesis by a dose-dependent transient braking of the 14 alpha-demethylase. Steroidogenesis is inhibited by its action on the C17-20 lyase, the cholesterol side-chain cleavage enzyme and the 17 alpha-hydroxylase. In gonads it inhibits aromatase and adrenocortical steroid biosynthesis is also inhibited at the 11 beta-hydroxylation and 18-hydroxylation steps. Its antiandrogenic effect may be useful in the management of metastatic prostate carcinoma and in testotoxicosis, its usefulness in the treatment of hirsutism is more questionable. Its anticortisolic effect may be useful in most Cushing's syndromes, where drug control of hypercortisolism is suitable for patients undergoing surgery, as well as those in whom more definitive treatment is delayed. Its usefulness as inhibitor of vitamin D or mineralocorticoids requires further investigation.
Service d'Endocrinologie-Diabétologie-Nutrition, Hôpital Jean Verdier, Bondy.
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D000311:Adrenal Glands / Q000187:drug effects* / Q000201:enzymology; D000446:Aldehyde-Lyases / Q000037:antagonists & inhibitors; D000726:Androgen Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004700:Endocrine System Diseases / Q000188:drug therapy; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000037:antagonists & inhibitors; D007654:Ketoconazole / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D010053:Ovary / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D013250:Steroid Hydroxylases / Q000037:antagonists & inhibitors; D013256:Steroids / Q000096:biosynthesis* / Q000494:pharmacology; D013737:Testis / Q000187:drug effects* / Q000201:enzymology
D000726:Androgen Antagonists; D013256:Steroids; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D000446:Aldehyde-Lyases; D007654:Ketoconazole; D006854:Hydrocortisone