Effect of in vitro ketoconazole on steroid production in rat testis.
In an attempt to confirm where in the testosterone (T) biosynthetic pathway of the rat testis ketoconazole (KTZ) inhibits T production, rat testicular mince was incubated with either 10 micrograms/ml or 100 micrograms/ml KTZ in the presence and absence of hCG (1 IU), and intratesticular pregnenolone (delta 5P), progesterone (P), 17-alpha-hydroxyprogesterone (17 alpha-HP), androstenedione (A) and testosterone (T) were assayed. In the absence of hCG, 10 micrograms/ml KTZ was sufficient to reduce intratesticular T by 80%. At this concentration of KTZ, intratesticular 17 alpha-HP (ng/g testis, mean +/- SEM) increased from 0.3 +/- 0.1 to 1.3 +/- 0.2 (p less than 0.0025), whereas intratesticular A decreased from 84 +/- 7 to 17 +/- 1 (p less than 0.005). KTZ did not inhibit the conversion of P to 17 alpha-HP. From these data it was concluded that KTZ has its inhibitory effect on testosterone biosynthesis in the rat testis primarily at the step catalyzed by the 17,20 desmolase enzyme.
D019326:17-alpha-Hydroxyprogesterone; D000735:Androstenedione / Q000096:biosynthesis; D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D006908:Hydroxyprogesterones / Q000096:biosynthesis; D007654:Ketoconazole / Q000494:pharmacology*; D008297:Male; D011284:Pregnenolone / Q000096:biosynthesis; D011374:Progesterone / Q000096:biosynthesis; D051381:Rats; D013737:Testis / Q000187:drug effects* / Q000378:metabolism; D013739:Testosterone / Q000096:biosynthesis*
D006063:Chorionic Gonadotropin; D006908:Hydroxyprogesterones; D013739:Testosterone; D000735:Androstenedione; D011374:Progesterone; D019326:17-alpha-Hydroxyprogesterone; D011284:Pregnenolone; D007654:Ketoconazole