ArticleJournal of molecular medicine (Berlin, Germany)2021
HIF2α regulates the synthesis and release of epinephrine in the adrenal medulla.
Article in Journal of molecular medicine (Berlin, Germany), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 11 citations in OpenAlex.
- Food allergy-induced anaphylaxis impairs adrenal adrenergic biosynthesis despite preserved vagal afferent-adrenal sympathetic reflex function.The journal of physiological sciences : JPS · 2026Article
- The Regulation of Catecholamine Biosynthesis by the Gas Transmitters Carbon Monoxide and Hydrogen Sulfide.Current issues in molecular biology · 2025Article
- The Immune Landscape of Pheochromocytoma and Paraganglioma: Current Advances and Perspectives.Endocrine reviews · 2024Review
- Sexual dimorphism during integrative endocrine and immune responses to ionizing radiation in mice.Scientific reports · 2024Article
- Dysregulation of hypoxia-inducible factor 1α in the sympathetic nervous system accelerates diabetic cardiomyopathy.Cardiovascular diabetology · 2023Article
- HIF and MYC signaling in adrenal neoplasms of the neural crest: implications for pediatrics.Frontiers in endocrinology · 2023Review
- Pseudohypoxia in paraganglioma and pheochromocytoma is associated with an immunosuppressive phenotype.The Journal of pathology · 2023Article
- Differential HIF2α Protein Expression in Human Carotid Body and Adrenal Medulla under Physiologic and Tumorigenic Conditions.Cancers · 2022Article
- Hypoxia signaling pathway: A central mediator in endocrine tumors.Frontiers in endocrinology · 2022Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The adrenal gland and its hormones regulate numerous fundamental biological processes; however, the impact of hypoxia signaling on adrenal function remains poorly understood. Here, we reveal that deficiency of HIF (hypoxia inducible factors) prolyl hydroxylase domain protein-2 (PHD2) in the adrenal medulla of mice results in HIF2α-mediated reduction in phenylethanolamine N-methyltransferase (PNMT) expression, and consequent reduction in epinephrine synthesis. Simultaneous loss of PHD2 in renal erythropoietin (EPO)-producing cells (REPCs) stimulated HIF2α-driven EPO overproduction, excessive RBC formation (erythrocytosis), and systemic hypoglycemia, which is necessary and sufficient to enhance exocytosis of epinephrine from the adrenal medulla. Based on these results, we propose that the PHD2-HIF2α axis in the adrenal medulla regulates the synthesis of epinephrine, whereas in REPCs, it indirectly induces the release of this hormone. Our findings are also highly relevant to the testing of small molecule PHD inhibitors in phase III clinical trials for patients with renal anemia. KEY MESSAGES: HIF2α and not HIF1α modulates PNMT during epinephrine synthesis in chromaffin cells. The PHD2-HIF2α-EPO axis induces erythrocytosis and hypoglycemia. Reduced systemic glucose facilitates exocytosis of epinephrine from adrenal gland.
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