Aldosterone secretion a molecular perspective. |
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Authors: | W C Boon J P Coghlan K M Curnow J G McDougall |
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Institution: | Howard Florey Institute of Experimental Physiology and Medicine, The University of Melbourne, Parkville, Victoria 3052, Australia. |
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Abstract: | The major mineralocorticoid hormone aldosterone is secreted from the zona glomerulosa of the adrenal cortex. Aldosterone is synthesized from cholesterol via a series of hydroxylations and oxidations. The enzymes involved in these reactions are mostly members of the cytochrome P450 superfamily. The final steps of this pathway, the conversion of 11-deoxycorticosterone (DOC) to aldosterone, require conversion via the intermediates 18-hydroxy-DOC or corticosterone and 18-hydroxycorticosterone. There are significant differences between species in the number of genes that encode the P450(11beta)-related enzymes (CYP11B) involved in these steps and the zonal distribution of their expression. One enzyme is capable of 11-hydroxylation, 18-hydroxylation, and 18-oxidation of DOC to aldosterone. The genetic basis of four diseases-congenital adrenal hyperplasia due to 11beta-hydroxylase deficiency, glucocorticoid-remediable aldosteronism, aldosterone synthase deficiency type I and type II-is explicable by mutations in these cytochrome P450(11beta)-related genes. (Trends Endocrinol Metab 1997;8:346-354). (c) 1997, Elsevier Science Inc. |
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