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Hair Loss Study Abstract: The effect of ketoconazole on steroidogenesis: I. Leydig cell enzyme activity in vitro.
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Title
The effect of ketoconazole on steroidogenesis: I. Leydig cell enzyme activity in vitro.
Author
Albertson BD; Frederick KL; Maronian NC; Feuillan P; Schorer S; Dunn JF; Loriaux DL
Address
Developmental Endocrinology Branch, NICHD, NIH, Bethesda, Maryland 20892.
Source
Res Commun Chem Pathol Pharmacol, 61: 1, 1988 Jul, 17-26
Abstract
The in vitro inhibition of Leydig cell microsomal steroidogenesis by ketoconazole, a
potent P-450 dependent enzyme blocker, was evaluated in the human, stallion and pig.
Purified Leydig cells were isolated by mechanical dispersion of teased, decapsulated whole
testes and sieving through a 0.25 mm stainless steel mesh. The activity of 3
beta-hydroxysteroid dehydrogenase/isomerase (3 beta-HSD), 17-hydroxylase (17-OHase),
17,20-desmolase (17,20D), 17-ketosteroid reductase (17-KSR) and aromatase were measured
using a constant amount (50 microM) of 14C-labelled substrates in the presence of varying
concentrations of pure ketoconazole. Products were isolated by thin layer chromatography
and verified by derivative formation. 17-OHase and 17,20D activities were significantly
inhibited (p less than .001) by ketoconazole at concentrations as low as 5 microM. 3
beta-HSD, 17-KSR and aromatase activities were only significantly inhibited by
ketoconazole at concentrations of 500 and 5000 microM. These data describe the specific
loci of inhibition of ketoconazole on testicular steroidogenesis and confirm the
observations that ketoconazole is an effective inhibitor of androgen biosynthesis in
several species.
Language of Publication
English
Unique Identifier
89018625
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