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

R L Barbieri, Robert L. Barbieri, Rapin Osathanondh, R Osathanondh, J A Canick, Jacob A. Canick, R J Stillman, Robert J. Stillman, K J Ryan, Kenneth J. Ryan
Steroids · 1980 · vol. 35(3) , pp. 251–263 · doi:10.1016/0039-128x(80)90038-0 · PMID:6966433 · W2075969942
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Danazol was found to inhibit human adrenal 21- and 11β-hydroxylase enzymes in vitro.

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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.

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MeSH descriptors

Adrenal Glands Danazol Pregnadienes Steroid 11-beta-Hydroxylase Steroid 21-Hydroxylase Steroid Hydroxylases Abortion, Legal Adrenal Glands Cytochrome P-450 Enzyme System Cytochrome P-450 Enzyme System Danazol Female Fetus Fetus Humans In Vitro Techniques Kinetics Microsomes Microsomes Mitochondria

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