The activity of five adrenocortical steroidogenic enzymes, 3β-hydroxysteroid dehydrogenase/isomerase (3β-HSD), 17-hydroxylase (17-OHase) 17,20 desmolase (17,20D), 21-hydroxylase (21-OHase) and 11-hydroxylase (11-OHase), were measured in vitro in purified mitochondria or microsomes from rhesus monkey (Macaca mulata) and human adrenal tissue in the presence and absence of graded concentrations of ketoconazole. Rhesus 3β-HSD activity was unaffected by ketoconazole at concentrations up to 5000 uM. However, human adrenal 3β-HSD was inhibited by approximately 40% (p<.01) at concentrations of 500 uM and by 80% at 100 uM. 17-OHase and 17,20D were significantly inhibited in the human at 5 uM (p<.001) and in the rhesus monkey at 50 uM (p<.001). A similar inhibitory effect was found on microsomal 21-OHase, with significant inhibition at 5 uM ketoconazole in the human and rhesus monkey (p<0.001). Mitochondrial 11-OHase was also significantly inhibited by ketoconazole in both the human (p<.005) and rhesus (p<.001) at 2.0 uM. These results represent documentation of the specific adrenal steroidogenic steps affected by ketoconazole and confirm the observations that this imidazole derivative is a powerful inhibitor of enzymes in the glucocorticoid pathway.
|Original language||English (US)|
|Number of pages||8|
|Journal||Research Communications in Chemical Pathology and Pharmacology|
|State||Published - Jan 1 1988|
ASJC Scopus subject areas
- Pathology and Forensic Medicine
- Pharmacology, Toxicology and Pharmaceutics(all)