Endocrinology and Metabolism, Kanazawa University Hospital, Kanazawa 920-8641, Japan.
Department of Hygiene, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-1192, Japan.
Int J Mol Sci. 2023 Mar 17;24(6):5782. doi: 10.3390/ijms24065782.
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.
醛固酮和皮质醇在心血管疾病和代谢紊乱的发病机制中起着重要作用。表观遗传学是一种通过不改变基因序列来控制基因表达的机制。甾体激素合成酶基因的表达受特定于每个基因的转录因子调控，已有报道称甲基化参与甾体激素的产生和疾病。血管紧张素 II 或钾调节醛固酮合酶基因，而促肾上腺皮质激素控制 11β-羟化酶。DNA 甲基化负调控 和 的表达，并对启动子基因的持续刺激做出动态变化的表达响应。醛固酮分泌性腺瘤中可见醛固酮合酶基因启动子区域的低甲基化状态。转录因子识别位点的甲基化，包括环磷腺苷反应元件结合蛋白 1 或神经生长因子诱导克隆 B，降低了它们的 DNA 结合活性。一种甲基化 CpG 结合蛋白 2 与甲基化的 CpG 二核苷酸直接合作。低盐饮食、血管紧张素 II 治疗和钾增加肾上腺中的 mRNA 水平并诱导 DNA 低甲基化。在库欣腺瘤和自主分泌皮质醇的醛固酮分泌性腺瘤中，低 DNA 甲基化比率与 表达增加之间存在密切关联。 或 的表观遗传控制在自主醛固酮或皮质醇合成中起着重要作用。
