Pathology of aldosterone biosynthesis and its action

Xin Gao, Yuto Yamazaki, Yuta Tezuka, Kei Omata, Yoshikiyo Ono, Ryo Morimoto, Yasuhiro Nakamura, Takashi Suzuki, Fumitoshi Satoh, Hironobu Sasano

Research output: Contribution to journalReview articlepeer-review

Abstract

Aldosterone plays pivotal roles in renin-angiotensin-aldosterone system in order to maintain the equilibrium of liquid volume and electrolyte metabolism. Aldosterone action is mediated by both mineralocorticoid receptor and 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). Its excessive actions directly induced tissue injuries in its target organs such as myocardial and vascular fibrosis in addition to chronic kidney diseases. Excessive aldosterone actions were also reported to be involved in unbalanced electrolyte metabolism in inflammatory bowel disease and development of pulmonary diseases. Hyperaldosteronism is tentatively classified into primary and secondary types. Primary aldosteronism is more frequent and has been well known to result in secondary hypertension with subsequent cardiovascular damages. Primary aldosteronism is also further classified into distinctive subtypes and among those, aldosterone-producing adenoma is the most frequent one accounting for the great majority of unilateral primary aldosteronism cases. In bilateral hyperaldosteronism, aldosterone-producing diffuse hyperplasia and aldosterone-producing micronodules or nodules are the major subtypes. All these aldosterone-producing lesions were reported to harbor somatic mutations including KCNJ5, CACNA1D, ATP1A1 and ATP2B3, which were all related to excessive aldosterone production. Among those mutations above, somatic mutation of KCNJ5 is the most frequent in aldosterone-producing adenoma and mostly composed of clear cells harboring abundant aldosterone synthase expression. In contrast, CACNA1D-mutated aldosterone-producing micronodules or aldosterone-producing nodules were frequently detected not only in primary aldosteronism patients but also in the zona glomerulosa of normal adrenal glands, which could eventually lead to an autonomous aldosterone production resulting in normotensive or overt primary aldosteronism, but their details have remained unknown.

Original languageEnglish
Pages (from-to)1-15
Number of pages15
JournalTohoku Journal of Experimental Medicine
Volume254
Issue number1
DOIs
Publication statusPublished - 2021

Keywords

  • 11β-hydroxysteroid dehydrogenase
  • Aldosterone
  • Mineralocorticoid receptor
  • Pathology
  • Primary aldosteronism

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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