Effect of trilostan on steroid excretion in man: compensated inhibition of 3 beta-hydroxysteroid dehydrogenase.
Trilostan (240, 360 and 480 mg/day administered p.o. to healthy men) induced an increase (P less than 0.05) in the urinary excretion rates of DHEA, androstenediol and pregnenolone but failed to influence the excretion rates of cortisol, aldosterone, and of the four glucocorticoid metabolites, THF, allo-THF, THE and allo-THE. A rise in plasma renin concentrations was seen in the initial phase of the trial. Administration of dexamethasone in addition to trilostan suppressed plasma and urinary concentrations of cortisol and the excretion rates of all estimated steroid metabolites but did not modify the relative abundance in the excretion rates of DHEA, androstenediol and pregnenolone. These results confirm that trilostan interferes with the activity of 3 beta-hydroxysteroid dehydrogenase in man. However, under physiological conditions production of cortisol and aldosterone is kept at a constant level, most likely by compensatory stimulation of the secretion of ACTH and renin.
D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D000328:Adult; D000450:Aldosterone / Q000378:metabolism; D015114:Androstenediol / Q000652:urine; D002849:Chromatography, Gas; D003687:Dehydroepiandrosterone / Q000652:urine; D003907:Dexamethasone / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D005938:Glucocorticoids / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D008297:Male; D011284:Pregnenolone / Q000652:urine; D012083:Renin / Q000097:blood; D013256:Steroids / Q000378:metabolism*
D005938:Glucocorticoids; D013256:Steroids; D013196:Dihydrotestosterone; D003687:Dehydroepiandrosterone; D000450:Aldosterone; D011284:Pregnenolone; D003907:Dexamethasone; D015114:Androstenediol; D015096:3-Hydroxysteroid Dehydrogenases; D012083:Renin; C009954:trilostane; D006854:Hydrocortisone