ALDOSTERONE SECRETION - A MOLECULAR PERSPECTIVE

The major mineralocorticoid hormone aldosterone is secreted from the z ona glomerulosa of the adrenal cortex. Aldosterone is synthesized from cholesterol via a series of hydroxylations and oxidations. The enzyme s involved in these reactions are mostly members of the cytochrome P45 0 superfamily. The final step of this pathway, the conversion of 11-de oxycorticosterone (DOC) to aldosterone, require conversion via the int ermediates 18-hydroxy-DOC or corticosterone and 18-hydroxycorticostero ne. There are significant differences between species in the number of genes that encode the P450(11 beta)-related enzymes (CYP11B) involved in these steps and the zonal distribution of their expression. One en zyme is capable of 11-hydroxylation, 18-hydroxylation, and 18-oxidatio n of DOC to aldosterone. The genetic basis of four diseases-congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency, glucocorti coid-remediable aldosteronism, aldosterone synthase deficiency type I and type II-is explicable by mutations in these cytochrome P450(11 bet a)-related genes. (C) 1997, Elsevier Science Inc.