Spironolactone and cytochrome P-450: impairment of steroid hydroxylation in the adrenal cortex

The effect of spironolactone administration on the content of adrenal microsomal cytochrome P-450 and on the activity of adrenal 17α-hydroxylase was examined in male cortisol and corticosterone-producing animals. Decreases in the content of microsomal cytochrome P-450 and in the activity of the 17α-hydroxylase after spironolactone treatment occur only in those animals which predominantly produce cortisol rather than corticosterone and which have a high activity of adrenal steroid 17α-hydroxylase. The administration of spironolactone to cortisol-producing animals, namely the guinea pig and the dog, caused a 50 to 80% loss of microsomal cytochrome P-450 with a concomitant decrease in the activity of the microsomal 17α-hydroxylase. In contrast to its effect in cortisol-producing animals, the administration of spironolactone caused either an increase or slight alteration in the concentration of adrenal microsomal cytochrome P-450 in corticosterone-producing animals such as the rat and the rabbit.