ArticleJournal of molecular endocrinology2016
Mutated KCNJ5 activates the acute and chronic regulatory steps in aldosterone production.
Article in Journal of molecular endocrinology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 41 citations in OpenAlex.
- Increased Frequency and Distinct Genotypic Patterns of Somatic Aldosterone-Driver Mutations in Aldosterone-Producing Micronodules from Primary Aldosteronism Patients.Endocrine pathology · 2026Article
- E3 ubiquitin ligase TRIM2 identified as a novel suppressor of CYP11B2 and aldosterone production.Cellular and molecular life sciences : CMLS · 2024Article
- Somatic SLC30A1 mutations altering zinc transporter ZnT1 cause aldosterone-producing adenomas and primary aldosteronism.Nature genetics · 2023Article
- Primary Aldosteronism: State-of-the-Art Review.American journal of hypertension · 2022Article
- Comprehensive Steroid Assay with Non-Targeted Analysis Using Liquid Chromatography Ion Mobility Mass Spectrometry.International journal of molecular sciences · 2022Article
- Genetics of Primary Aldosteronism.Hypertension (Dallas, Tex. : 1979) · 2022Review
- Genetic Alterations in Benign Adrenal Tumors.Biomedicines · 2022Review
- Rapidity and Precision of Steroid Hormone Measurement.Journal of clinical medicine · 2022Review
- Aromatase and nonaromatase neurons in the zebra finch secondary auditory forebrain are indistinct in their song-driven gene induction and intrinsic electrophysiological properties.The European journal of neuroscience · 2021Article
- Pathophysiological and Pharmacological Characteristics ofBiomedicines · 2021Article
- Molecular Mechanisms of Functional Adrenocortical Adenoma and Carcinoma: Genetic Characterization and Intracellular Signaling Pathway.Biomedicines · 2021Review
- GENETICS IN ENDOCRINOLOGY: Impact of race and sex on genetic causes of aldosterone-producing adenomas.European journal of endocrinology · 2021Review
- Update on Genetics of Primary Aldosteronism.Biomedicines · 2021Review
- Aldosterone-Regulating Receptors and Aldosterone-Driver Somatic Mutations.Frontiers in endocrinology · 2021Article
- Pathogenesis and treatment of primary aldosteronism.Nature reviews. Endocrinology · 2020Review
- Use of Steroid Profiling Combined With Machine Learning for Identification and Subtype Classification in Primary Aldosteronism.JAMA network open · 2020Article
- Genetic, Cellular, and Molecular Heterogeneity in Adrenals With Aldosterone-Producing Adenoma.Hypertension (Dallas, Tex. : 1979) · 2020Article
- Molecular and Electrophysiological Analyses of ATP2B4 Gene Variants in Bilateral Adrenal Hyperaldosteronism.Hormones & cancer · 2020Article
- Primary aldosteronism diagnostics:Gland surgery · 2020Review
- Steroid Metabolome Analysis in Disorders of Adrenal Steroid Biosynthesis and Metabolism.Endocrine reviews · 2019Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Somatic and germline mutations in the inward-rectifying K(+) channel (KCNJ5) are a common cause of primary aldosteronism (PA) in aldosterone-producing adenoma and familial hyperaldosteronism type III, respectively. Dysregulation of adrenal cell calcium signaling represents one mechanism for mutated KCNJ5 stimulation of aldosterone synthase (CYP11B2) expression and aldosterone production. However, the mechanisms stimulating acute and chronic production of aldosterone by mutant KCNJ5 have not been fully characterized. Herein, we defined the effects of the T158A KCNJ5 mutation (KCNJ5(T158A)) on acute and chronic regulation of aldosterone production using an adrenal cell line with a doxycycline-inducible KCNJ5(T158A) gene (HAC15-TRE-KCNJ5(T158A)). Doxycycline incubation caused a time-dependent increase in KCNJ5(T158A) and CYP11B2 mRNA and protein levels. Electrophysiological analyses confirm the loss of inward rectification and increased Na(+) permeability in KCNJ5(T158A)-expressing cells. KCNJ5(T158A) expression also led to the activation of CYP11B2 transcriptional regulators, NURR1 and ATF2. Acutely, KCNJ5(T158A) stimulated the expression of total and phosphorylated steroidogenic acute regulatory protein (StAR). KCNJ5(T158A) expression increased the synthesis of aldosterone and the hybrid steroids 18-hydroxycortisol and 18-oxocortisol, measured with liquid chromatography-tandem mass spectrometry (LC-MS/MS). All of these stimulatory effects of KCNJ5(T158A) were inhibited by the L-type Ca(2+) channel blocker, verapamil. Overall, KCNJ5(T158A)increases CYP11B2 expression and production of aldosterone, corticosterone and hybrid steroids by upregulating both acute and chronic regulatory events in aldosterone production, and verapamil blocks KCNJ5(T158A)-mediated pathways leading to aldosterone production.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.