Aldosterone, not only an adrenal mineralocorticoid: An updated review of its functions, mechanisms, biosynthesis, hormone system and regulation in multiple organs and tissues.

Aldosterone, the principal mineralocorticoid, is critical for regulating electrolyte balance and blood pressure through its interaction with mineralocorticoid receptor (MR). This review traces the historical evolution of aldosterone research, from its discovery in the 1950s to current insights into its biosynthesis and signaling mechanisms. It details the enzymatic pathways of aldosterone production, emphasizing the role of cytochrome P450 11β2 (CYP11B2) in both adrenal and extra-adrenal tissues, and elucidates the structural basis for its specificity. The physiological roles of aldosterone are explored, highlighting its regulation of ion transport proteins and its impact on cardiovascular health, including vascular remodeling and myocardial fibrosis. The review examines the complex signaling pathways activated by aldosterone, encompassing MR-dependent genomic and non-genomic effects, as well as MR-independent mechanisms. It also addresses aldosterone-independent MR activation by glucocorticoids under conditions of reduced 11β hydroxysteroid dehydrogenase type 2 (11β-HSD2) expression. Furthermore, the review consolidates findings on regulatory factors influencing aldosterone synthesis, such as the renin-angiotensin-aldosterone system, adrenocorticotropic hormone, potassium, sodium, and glucose levels, emphasizing systemic and local regulation, as a foundation for future clinical interventions in disorders associated with dysregulated aldosterone signaling.