Stölting Gabriel, Scholl Ute I
Center of Functional Genomics, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany.
Handb Exp Pharmacol. 2024;283:59-79. doi: 10.1007/164_2023_680.
The mineralocorticoid aldosterone is produced in the zona glomerulosa of the adrenal cortex. Its synthesis is regulated by the serum concentrations of the peptide hormone angiotensin II and potassium. The primary role of aldosterone is to control blood volume and electrolytes. The autonomous production of aldosterone (primary aldosteronism, PA) is considered the most frequent cause of secondary hypertension. Aldosterone-producing adenomas and (micro-)nodules are frequent causes of PA and often carry somatic mutations in ion channels and transporters. Rare familial forms of PA are due to germline mutations. Both somatic and germline mutations in the chloride channel gene CLCN2, encoding ClC-2, have been identified in PA. Clinical findings and results from cell culture and animal models have advanced our knowledge about the role of anions in PA. The zona glomerulosa of the adrenal gland has now been firmly established as a tissue in which anions play a significant role for signaling. In this overview, we aim to summarize the current knowledge and highlight novel concepts as well as open questions.
盐皮质激素醛固酮由肾上腺皮质球状带产生。其合成受肽类激素血管紧张素II和钾的血清浓度调节。醛固酮的主要作用是控制血容量和电解质。醛固酮自主分泌(原发性醛固酮增多症,PA)被认为是继发性高血压最常见的病因。醛固酮瘤和(微)结节是PA的常见病因,且常在离子通道和转运体中携带体细胞突变。PA的罕见家族形式是由种系突变引起的。在PA中已鉴定出编码ClC-2的氯离子通道基因CLCN2的体细胞和种系突变。临床发现以及细胞培养和动物模型的结果增进了我们对阴离子在PA中作用的认识。肾上腺球状带现已被确认为阴离子在信号传导中起重要作用的组织。在本综述中,我们旨在总结当前的知识,突出新的概念以及未解决的问题。