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  • Title: The effect of ketoconazole on adrenal and testicular steroidogenesis in vitro.
    Author: Lambert A, Mitchell R, Robertson WR.
    Journal: Biochem Pharmacol; 1986 Nov 15; 35(22):3999-4004. PubMed ID: 3022746.
    Abstract:
    The effect of the anti-fungal agent, ketoconazole, on cortisol secretion from adrenal cells stimulated with ACTH (1-24, 50 ng/l) and on testosterone secretion from Leydig cells stimulated with LH (5 i.u./l), has been tested. The concentration of drug which inhibited cortisol and testosterone secretion by 50% (ED50) was 3.6 +/- 0.7 mumol/l and 0.61 +/- 0.03 mumol/l, respectively. The effect of ketoconazole on adrenal and testicular steroidogenesis was completely reversible. Thus, adrenal and testicular cells which had been washed after exposure to greater than 95% inhibitory dose of ketoconazole responded in a similar manner to hormone stimulation as cells similarly washed and which had not been exposed to drug. The sites of the anti-steroidogenic effect of ketoconazole have been established using a method based upon the sequential stimulation by the exogenous precursor steroids of the various steps leading to the biosynthesis of cortisol by adrenal cells and testosterone by Leydig cells. We conclude that ketoconazole reversibly inhibits the sequence between ACTH/LH binding and pregnenolone production and also inhibits testicular C-17-C-20, lyase activity.
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