Molecular mechanism of cytochrome P-450-dependent aldosterone biosynthesis in the adrenal cortex

Abstract

In the adrenal cortex, the potent mineralocorticoid, aldosterone, is produced in the zoba glomerulosa but not in the zona fasciculata/reticularis. In rodents and humans, two distinct species of P-450 C18 (aldosterone synthase) and P-450 11β (11β-hydroxylase) are expressed in the adrenal cortex. The selective expression of cytochrome P-450 species in different zones contributes to zone specificity of aldosterone synthesis. In the cow and pig, only one molecular species of P-450 11β having both 11β-hydroxylase and aldosterone synthase activity is expressed throughout the adrenal cortex. P-450 11β in the zona fasciculata/reticularis catalyzes the formation of corticosterone but not that of aldosterone from 11-deoxycorticosterone; the same enzyme in the zona glomerulosa produces aldosterone from the same substrate, indicating that a local factor in mitochondria is likely to be involved in the selective suppression of the aldosterone synthetic activity of P-450 11β in the zona fasciculata/reticularis. The zone specificity of aldosterone synthesis catalyzed by P-450 11β in the bovine adrenal cortex appears to be due to differences in interactions between P-450 11β and P-450 SCC in mitochondria in different cortical zones. Thus, two modes exist for aldosterone biosynthesis in mammals: rodent-human and bovine-porcine modes.