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Extra-adrenal aldosterone: a mini review focusing on the physiology and pathophysiology of intrarenal aldosterone

  • Mini Review
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Abstract

Purpose

Accumulating evidence has demonstrated the existence of extra-adrenal aldosterone in various tissues, including the brain, heart, vascular, adipocyte, and kidney, mainly based on the detection of the CYP11B2 (aldosterone synthase, cytochrome P450, family 11, subfamily B, polypeptide 2) expression using semi-quantitative methods including reverse transcription-polymerase chain reaction and antibody-based western blotting, as well as local tissue aldosterone levels by antibody-based immunosorbent assays. This mini-review highlights the current evidence and challenges in extra-adrenal aldosterone, focusing on intrarenal aldosterone.

Methods

A narrative review.

Results

Locally synthesized aldosterone may play a vital role in various physio-pathological processes, especially cardiovascular events. The site of local aldosterone synthesis in the kidney may include the mesangial cells, podocytes, proximal tubules, and collecting ducts. The synthesis of renal aldosterone may be regulated by (pro)renin receptor/(pro)renin, angiotensin II/Angiotensin II type 1 receptor, wnt/β-catenin, cyclooxygenase-2/prostaglandin E2, and klotho. Enhanced renal aldosterone release promotes Na+ reabsorption and K+ excretion in the distal nephron and may contribute to the progress of diabetic nephropathy and salt-related hypertension.

Conclusions

Inhibition of intrarenal aldosterone signaling by aldosterone synthase inhibitors or mineralocorticoid receptor antagonists may be a hopeful pharmacological technique for the therapy of diabetic nephropathy and saltrelated hypertension. Yet, current reports are often conflicting or ambiguous, leading many to question whether extra-adrenal aldosterone exists, or whether it is of any physiological and pathophysiological significance.

Highlights

  • Local aldosterone synthesis may present in extra-adrenal tissues like the kidneys and play significant physiological and pathophysiological significance.

  • Wnt/β-catenin pathway interacts with PRR/sPRR contributing to intrarenal aldosterone synthesis by activating intrarenal RAS.

  • COX-2/PGE2/EP1 pathway stimulates intrarenal aldosterone production by activating sPRR/β-catenin signaling.

  • Intrarenal aldosterone may contribute to Na+/K+ homeostasis, kidney injury, and salt-related hypertension.

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Acknowledgements

I thank Ms. Huiru Yang for technical assistance.

Funding

This work was supported by the National Natural Science Foundation of China (Nos. 32100908 and 82160051), the Jiangxi Provincial Natural Science Foundation (Nos. 20212BAB216005 and 20232BAB206018), PhD Start-up Research Fund in Jiangxi University of Chinese Medicine (No. 2020BSZR009), Jiangxi “Double thousand plan” (No. jxsq2020101074), the science and technology research project in Education Department of Jiangxi Province (No. GJJ2200904), the science and technology research project in Health Commission of Jiangxi Province (No. 202311143), Jiangxi Key Laboratory grant in Science and Technology Department of Jiangxi Province (No. 20202BCD42014), and the Scientific and Technological Innovation Team grant of Jiangxi University of Chinese Medicine (No. CXTD22014).

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    Chuanming Xu

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Xu, C. Extra-adrenal aldosterone: a mini review focusing on the physiology and pathophysiology of intrarenal aldosterone. Endocrine 83, 285–301 (2024). https://doi.org/10.1007/s12020-023-03566-6

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