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Danazol inhibits human adrenal 21-and 11 beta-hydroxylation in vitro.
- Source :
-
Steroids [Steroids] 1980 Mar; Vol. 35 (3), pp. 251-63. - Publication Year :
- 1980
-
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.
- Subjects :
- Abortion, Legal
Cytochrome P-450 Enzyme System metabolism
Female
Fetus metabolism
Humans
In Vitro Techniques
Kinetics
Microsomes metabolism
Mitochondria metabolism
Pregnancy
Spectrophotometry
Adrenal Glands metabolism
Danazol pharmacology
Pregnadienes pharmacology
Steroid 11-beta-Hydroxylase antagonists & inhibitors
Steroid 21-Hydroxylase antagonists & inhibitors
Steroid Hydroxylases antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 0039-128X
- Volume :
- 35
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Steroids
- Publication Type :
- Academic Journal
- Accession number :
- 6966433
- Full Text :
- https://doi.org/10.1016/0039-128x(80)90038-0