Danazol inhibits steroidogenesis in the rat testis in vitro.
The effects of danazol on steroidogenesis in vitro in the rat testis were examined by studying: 1) androgen synthesis in rat Leydig cells cultured with danazol, 2) danazol binding to rat testis microsomal cytochrome P-450, and 3) enzyme kinetics of danazol inhibition of the microsomal enzymes of testicular steroidogenesis. Concentrations of danazol as low as 1 micrometer suppressed LH-stimulated testosterone and androstenedione production in cultured Leydig cells. The addition of danazol to a preparation of testicular microsomes elicited a type I cytochrome P-450 binding spectrum, with an apparent spectral dissociation constant (Ks) of 4.8 micrometer. Danazol inhibited progesterone and 17alpha-hydroxy-progesterone binding to microsomal P-450 with apparent spectral inhibition constants of 2.4 micrometer and 2.8 micrometer, respectively. Danazol competitively inhibited 3beta-hydroxy-delta5-steroid dehydrogenase-isomerase (apparent enzymatic inhibition constant, KI = 5.8 micrometer), 17alpha-hydroxylase (KI = 2.4 micrometer), 17,20 lyase (KI = 1.9 micrometer), and 17beta-hydroxysteroid dehydrogenase (KI = 4.4 micrometer). These findings indicate that low concentrations of danazol directly inhibit steroidogenesis in the rat testis in vitro.
D000728:Androgens / Q000096:biosynthesis*; D000818:Animals; D003613:Danazol / Q000494:pharmacology*; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism; D007700:Kinetics; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism; D007986:Luteinizing Hormone / Q000494:pharmacology; D008297:Male; D008861:Microsomes / Q000378:metabolism; D011245:Pregnadienes / Q000494:pharmacology*; D051381:Rats; D013053:Spectrophotometry; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism; D013737:Testis / Q000187:drug effects / Q000378:metabolism*
D000728:Androgens; D011245:Pregnadienes; D007986:Luteinizing Hormone; D006913:Hydroxysteroid Dehydrogenases; D013254:Steroid 17-alpha-Hydroxylase; D003613:Danazol