PMID: 6966433Mar 1, 1980Paper

Danazol inhibits human adrenal 21-and 11 beta-hydroxylation in vitro

Steroids
R L BarbieriK J Ryan

Abstract

The effects of danazol on steroidogenesis in vitro in the 16-20 week old human fetal adrenal were examined by studying: 1) danazol binding to adrenal microsomal and mitochondrial cytochrome P-450, and 2) enzyme kinetics of danazol inhibition of the adrenal microsomal 21-hydroxylase and the mitochondrial 11 beta-hydroxylase. The addition of danazol to preparations of adrenal microsomes or mitochondria elicited a type I cytochrome P-450 binding spectrum. Danazol bound to microsomal cytochrome P-450 binding spectrum. Danazol bound to microsomal cytochrome P-450 with a high affinity apparent spectral dissociation constant (KS) of 1 microM and with a lower affinity K's of 10 microM. Danazol bound to mitochondrial cytochrome P-450 with a KS of 5 microM. In addition, danazol competitively inhibited the microsomal 21-hydroxylase (apparent enzymatic inhibition constant KI = 0.8 microM) and the mitochondrial 11 beta-hydroxylase (KI = 3 microM). These findings demonstrate that low concentrations of danazol directly inhibit steroidogenesis in the human fetal adrenal in vitro.

References

Jan 1, 1975·Life Sciences·P K Zachariah, M R Juchau
Nov 1, 1975·Fertility and Sterility·A C WentzT M King
Dec 1, 1977·Endocrinology·R L BarbieriK J Ryan
Dec 23, 1976·The New England Journal of Medicine·J A GelfandM M Frank
Jan 15, 1977·American Journal of Obstetrics and Gynecology·R H Asch, R B Greenblatt
Dec 1, 1975·American Journal of Obstetrics and Gynecology·N H LauersenS Birnbaum
Feb 1, 1971·Fertility and Sterility·R B GreenblattH F Scholer
Oct 1, 1966·The Journal of Clinical Endocrinology and Metabolism·C E BirdS Solomon

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Citations

Apr 1, 1981·Journal of Steroid Biochemistry·R L BarbieriK J Ryan
Jul 1, 1985·Journal of Steroid Biochemistry·M T GordonW R Robertson
Sep 12, 2002·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Vincenzo De LeoFelice Petraglia
Feb 1, 1990·American Journal of Obstetrics and Gynecology·R L Barbieri

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