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Selective inhibition of aldosterone production modulates human adrenocortical (HAC15) cell fate

Long KC 1 , Aminuddin A 1 , Ajlaa Ayub N 2 , Tan GC 2 , Jamal ARA 3 , Abdul Murad NA 3 Show all authors , Johdi NA 3 , Gomez-Sanchez CE 4 , Sukor N 1 , Brown MJ 5 , Azizan EA 1

Affiliations 

  • 1 Department of Medicine, Faculty of Medicine, The National University of Malaysia (UKM), Kuala Lumpur, Malaysia
  • 2 Department of Pathology, Faculty of Medicine, The National University of Malaysia (UKM), Kuala Lumpur, Malaysia
  • 3 UKM Medical Molecular Biology Institute (UMBI), The National University of Malaysia (UKM), Kuala Lumpur, Malaysia
  • 4 Gordon V. (Sonny) Montgomery Veterans Affairs Medical Center and Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, United States
  • 5 William Harvey Research Institute, Queen Mary University of London, London, United Kingdom
Front Endocrinol (Lausanne), 2026;17:1872432.
PMID: 42935676 DOI: 10.3389/fendo.2026.1872432

Abstract

BACKGROUND: Aldosterone, produced in the zona glomerulosa (ZG) by aldosterone synthase (CYP11B2), regulates sodium balance and blood pressure. In adult adrenals, CYP11B2-expressing ZG cells are sparse, likely reflecting chronic suppression of the renin-angiotensin system under high-salt conditions. Whether reduced aldosterone synthesis directly influences ZG cell behavior remains unclear. This study examined the impact of CYP11B2 inhibition on human adrenal cell fate and function.

METHODS: CYP11B2 was inhibited in HAC15 cells using siRNA (siCYP11B2) or baxdrostat, a selective CYP11B2 inhibitor. Forty-eight hours post-treatment, steroid hormone levels, RNA sequencing profiles, and functional outputs (EZMTT metabolic assay, xCELLigence real-time cell analysis, and Annexin V/SYTOX flow cytometry for apoptosis/necrosis) were evaluated.

RESULTS: siCYP11B2 reduced aldosterone production by 70% ± 2.9% (n = 18, p 

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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