Effect of adrenalectomy on the substrate interaction with cytochrome P-450 in the hydroxylation of steroid hormones by liver microsomes.

Abstract

Adrenalectomy in male rats slightly decreased cytochrome P-450 content in liver microsomes. The magnitude of testosterone-induced spectral change and the hydroxylating activity for testosterone by liver microsomes were markedly decreased to a similar extent in adrenalectomized male rats. Similar results were obtained, when progesterone was used as the substrate. The magnitude of testosterone-or progesteroneinduced spectral change per unit of P-450 was also decreased in the adrenalectomized males. These results suggest that the binding capacity of cytochrome P-450 for testosterone or progesterone was decreased after adrenalectomy.In contrast to the results obtained with male rats, the binding capacity of cytochrome P-450 and the hydroxylating activity for testosterone or progesterone were not significantly decreased in the adrenalectomized females. Similarly, the binding capacity of P-450 and the hydroxylating activity for testosterone or progesterone were not significantly decreased by adrenalectomy in castrated male rats and male and female mice. However, adrenalectomy in castrated and testosterone-treated male rats produced the effects similar to those observed in the intact male rats.These results indicate that the action of androgen to increase the binding capacity of cytochrome P-450 for steroid hormone was impaired in the adrenalectomized rats and consequently the hydroxylating activity for steroid hormones by liver microsomes was decreased.