Tohoku J. Exp. Med., 2021 May, 254(1)

Invited Review for the 100th Anniversary of the TJEM

Pathology of Aldosterone Biosynthesis and its Action

Xin Gao,1 Yuto Yamazaki,1 Yuta Tezuka,2,3 Kei Omata,2,3Yoshikiyo Ono,3 Ryo Morimoto,3 Yasuhiro Nakamura,4 Takashi Suzuki,5 Fumitoshi Satoh2,3 and Hironobu Sasano1

1Department of Pathology, Tohoku University, Graduate School of Medicine, Sendai, Miyagi, Japan
2Division of Clinical Hypertension, Endocrinology and Metabolism, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
3Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Hospital, Sendai, Miyagi, Japan
4Division of Pathology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi, Japan
5Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

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.

Key words —— aldosterone; 11β-hydroxysteroid dehydrogenase; mineralocorticoid receptor; pathology; primary aldosteronism

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Tohoku J. Exp. Med 2021, 254, 1-15.

Correspondence: Hironobu Sasano, M.D., Ph.D., Department of Pathology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980- 8575, Japan.

e-mail: hsasano@patholo2.med.tohoku.ac.jp