Chronic activation of adrenal Gq signaling induces Cyp11b2 expression in the zona fasciculata and hyperaldosteronism.

Autor: van Rooyen D; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA; Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA., Lerario AM; Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA., Little DW 3rd; Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA., Ullenbruch MR; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA., Taylor MJ; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA., Gomez-Sanchez CE; Endocrine Section, G.V. (Sonny) Montgomery VA Medical Center and the Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, USA., Hammer GD; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA; Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA; Department of Cell and Development Biology, University of Michigan, Ann Arbor, MI, USA., Rainey WE; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA; Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA. Electronic address: wer@umich.edu.
Jazyk: angličtina
Zdroj: Molecular and cellular endocrinology [Mol Cell Endocrinol] 2024 May 01; Vol. 585, pp. 112176. Date of Electronic Publication: 2024 Feb 08.
DOI: 10.1016/j.mce.2024.112176
Abstrakt: Hyperaldosteronism is often associated with inappropriate aldosterone production and aldosterone synthase (Cyp11b2) expression. Normally, Cyp11b2 expression is limited to the adrenal zona glomerulosa (ZG) and regulated by angiotensin II which signals through Gq protein-coupled receptors. As cells migrate inwards, they differentiate into 11β-hydroxylase-expressing zona fasciculata (ZF) cells lacking Cyp11b2. The mechanism causing ZG-specific aldosterone biosynthesis is still unclear. We investigated the effect of chronic Gq signaling using transgenic mice with a clozapine N-oxide (CNO)-activated human M3 muscarinic receptor (DREADD) coupled to Gq (hM3Dq) that was expressed throughout the adrenal cortex. CNO raised circulating aldosterone in the presence of a high sodium diet with greater response seen in females compared to males. Immunohistochemistry and transcriptomics indicated disrupted zonal Cyp11b2 expression while Wnt signaling remained unchanged. Chronic Gq-DREADD signaling also induced an intra-adrenal RAAS in CNO-treated mice. Chronic Gq signaling disrupted adrenal cortex zonal aldosterone production associated with ZF expression of Cyp11b2.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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