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  1. Fulltext Selective inhibition of aldosterone production modulates human adrenocortical (HAC15) cell fate
    Long KC, Aminuddin A, Ajlaa Ayub N, Tan GC, Jamal ARA, Abdul Murad NA, et al.
    Front Endocrinol (Lausanne), 2026;17:1872432.
    PMID: 42935676 DOI: 10.3389/fendo.2026.1872432
    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 

  2. Fulltext Somatic mutations of GNA11 and GNAQ in CTNNB1-mutant aldosterone-producing adenomas presenting in puberty, pregnancy or menopause
    Zhou J, Azizan EAB, Cabrera CP, Fernandes-Rosa FL, Boulkroun S, Argentesi G, et al.
    Nat Genet, 2021 Sep;53(9):1360-1372.
    PMID: 34385710 DOI: 10.1038/s41588-021-00906-y
    Most aldosterone-producing adenomas (APAs) have gain-of-function somatic mutations of ion channels or transporters. However, their frequency in aldosterone-producing cell clusters of normal adrenal gland suggests a requirement for codriver mutations in APAs. Here we identified gain-of-function mutations in both CTNNB1 and GNA11 by whole-exome sequencing of 3/41 APAs. Further sequencing of known CTNNB1-mutant APAs led to a total of 16 of 27 (59%) with a somatic p.Gln209His, p.Gln209Pro or p.Gln209Leu mutation of GNA11 or GNAQ. Solitary GNA11 mutations were found in hyperplastic zona glomerulosa adjacent to double-mutant APAs. Nine of ten patients in our UK/Irish cohort presented in puberty, pregnancy or menopause. Among multiple transcripts upregulated more than tenfold in double-mutant APAs was LHCGR, the receptor for luteinizing or pregnancy hormone (human chorionic gonadotropin). Transfections of adrenocortical cells demonstrated additive effects of GNA11 and CTNNB1 mutations on aldosterone secretion and expression of genes upregulated in double-mutant APAs. In adrenal cortex, GNA11/Q mutations appear clinically silent without a codriver mutation of CTNNB1.
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