Inhibition of human placental progesterone synthesis by danazol in vitro

In vitro, danazol showed a slight dose-dependent inhibition of the mitochondrial cholesterol side chain cleavage enzyme isolated from early gestational (8th to 12th week of gestation) placenta. In the presence of 100 microM danazol, the enzyme activity was 65% of controls. Danazol inhibits dose-dependently the mitochondrial 3 beta-hydroxysteroid dehydrogenase (I50 = 3.1 microM; Ki = 1 microM) (noncompetitive inhibition) and the cytoplasmic 20 alpha-hydroxysteroid dehydrogenase (I50 = 1.4 microM; Ki = 2.6 microM) (competitive inhibition). The inhibition of human placental progesterone synthesis by danazol in vitro is a further example for the direct interference of danazol with steroidogenesis.