Synthesis of 18-hydroxycortisol and 18-oxocortisol in bovine adrenal zona glomerulosa mitochondria.

The biosynthesis of 18-hydroxycortisol and 18-oxocortisol from cortisol was studied in calf adrenal zona glomerulosa mitochondria. Cortisol is converted to 18-hydroxycortisol and 18-oxocortisol in the same mitochondrial preparation in which corticosterone is metabolized to 18-hydroxycorticosterone and aldosterone. Cortisol and 18-hydroxycortisol interacted with mitochondria to cause a Type I differential spectrum, which was decreased by sodium dithionite. The metabolism of cortisol to 18-hydroxycortisol and 18-oxocortisol was inhibited by metyrapone in a competitive way. Cortisol was a competitive inhibitor of the transformation of corticosterone into 18-hydroxycorticosterone and aldosterone, and corticosterone was a competitive inhibitor of the transformation of cortisol into 18-hydroxycortisol and 18-oxocortisol, with a Ki very similar to the Km for the transformation of that steroid to aldosterone. These results indicate that cortisol is metabolized to 18-hydroxycortisol and 18-oxocortisol by a mitochondrial cytochrome P-450, which is the same as that which catalyzes the conversion of corticosterone into aldosterone.