Interaction of androgens with the adrenal mitochondrial cytochrome system. The influence of androgen treatment on the levels of cytochrome in rat adrenal cortical mitochondria and on substrate-induced spectral changes

The treatment of female rats with high doses of the synthetic androgens, 17α-methylandrostenediol (MAD) and 17α-methyltestosterone (MT), leads to inhibition of corticosterone formation from progesterone in adrenal homogenates. Mitochondria were isolated from the adrenals of control and treated animals and several changes were noted. 11β-Hydroxylation rates were about 40 and 70% of control rates in adrenal mitochondria from MT- and MAD-treated rats, respectively. Associated with the androgen treatment there was a doubling in the levels of cytochromes a and a₃ in the adrenal mitochondria with no change in the levels of cytochromes b or c and c₁. The cytochrome P-450 levels were about 60% of control levels in adrenal mitochondria isolated from MT- and MAD-treated rats. In addition to these alterations in adrenal mitochondria cytochrome levels, there was evidence that the MT was bound to the adrenal mitochondria. This binding resulted in lower DOC-induced spectral changes in adrenal mitochondria isolated from MT-treated rats. Such binding of androgen and the lower levels of cytochrome P-450 would appear to explain the decreased 11β-hydroxylation rates.