Molecular and Epigenetic Control of Aldosterone Synthase, CYP11B2 and 11-Hydroxylase, CYP11B1.

Aldosterone and cortisol serve important roles in the pathogenesis of cardiovascular diseases and metabolic disorders. Epigenetics is a mechanism to control enzyme expression by genes without changing the gene sequence. Steroid hormone synthase gene expression is regulated by transcription factors specific to each gene, and methylation has been reported to be involved in steroid hormone production and disease. Angiotensin II or potassium regulates the aldosterone synthase gene, . The adrenocorticotropic hormone controls the 11b-hydroxylase, . DNA methylation negatively controls the and expression and dynamically changes the expression responsive to continuous stimulation of the promoter gene. Hypomethylation status of the promoter region is seen in aldosterone-producing adenomas. Methylation of recognition sites of transcription factors, including cyclic AMP responsive element binding protein 1 or nerve growth factor-induced clone B, diminish their DNA-binding activity. A methyl-CpG-binding protein 2 cooperates directly with the methylated CpG dinucleotides of . A low-salt diet, treatment with angiotensin II, and potassium increase the mRNA levels and induce DNA hypomethylation in the adrenal gland. A close association between a low DNA methylation ratio and an increased expression is seen in Cushing's adenoma and aldosterone-producing adenoma with autonomous cortisol secretion. Epigenetic control of or plays an important role in autonomic aldosterone or cortisol synthesis.