The effect of ketoconazole on steroidogenesis. II. Adrenocortical enzyme activity in vitro

B. D. Albertson, N. C. Maronian, K. L. Frederick, M. DiMattina, P. Feuillan, J. F. Dunn, D. L. Loriaux

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10 Scopus citations


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 languageEnglish (US)
Pages (from-to)27-34
Number of pages8
JournalResearch Communications in Chemical Pathology and Pharmacology
Issue number1
StatePublished - 1988
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Toxicology
  • Pharmacology
  • Pharmacology, Toxicology and Pharmaceutics(all)


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