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 long-term therapeutic targeting.