Danazol Inhibits Human Adrenal 21- and 11β-Hydroxylation in vitro

Article abstract of DOI:10.1016/0039-128X(80)90038-0

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 11β-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 with a high affinity apparent spectral dissociation constant (K_S) of 1 μM and with a lower affinity K'_S of 10 μM.Danazol bound to mitochondrial cytochrome P-450 with a K_S of 5 μM.In addition, danazol competitively inhibited the microsomal 21-hydroxylase (apparent enzymatic inhibition constant K_I = 0.8 μM) and the mitrochondrial 11β-hydroxylase (K_I = 3 μM).These findings demonstrate that low concentrations of danazol directly inhibit steroidogenesis in the human fetal adrenal in vitro.