ECE2022 Poster Presentations Adrenal and Cardiovascular Endocrinology (87 abstracts)
HIF-2α is detrimental for the functioning of the adrenal medulla
Deepika Watts 1 , Nicole Bechmann 1,2 , Hermine Mohr 3 , Anja Krüger 1 , Natalia S. Pellegata 3 , Graeme Eisenhofer 1 , Mirko Peitzsch 1 & Ben Wielockx 1
1Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; 2Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; 3Institute for Diabetes and Cancer, Helmholtz Zentrum München, Neuherberg, Germany
The adrenal gland is a crucial regulator of numerous fundamental biological processes and its hormones are essential for maintaining homeostasis in normal and stressful situations. However, the impact of hypoxia signalling on the function of the adrenal remains poorly understood. During the past years, our research group has focused on enhancing our understanding of hypoxia pathway proteins (HPPs) in the different areas of the adrenal gland. Firstly, we described a crucial role for hypoxia inducible factor-1 α (HIF-1α) during adrenal steroidogenesis (Watts et al., CMLS, 2021) and secondly, we demonstrated that HIF-2α is essential for the synthesis and release of catecholamines. Briefly, HIF-2α stabilization due to loss of prolyl hydroxylase domain protein-2 (PHD2) leads to reduced phenylethanolamine N-methyltransferase (PNMT) activity and consequent epinephrine synthesis. Simultaneously, HIF-2α mediated erythropoietin (EPO) production in renal EPO producing cells (REPCs) stimulated excessive RBC formation (erythrocytosis) leading to hypoglycaemia and increased release of epinephrine from the adrenal medulla (Watts et al., JMM, 2021). Recently, we generated a new set of mouse lines efficiently targeting the HPPs in chromaffin cells to further unravel the impact of HIF-2α -stabilisation during the development of medulla-related tumours. This will provide us with an excellent chance to enhance our current knowledge on potential targets for the therapeutic treatment of pheochromocytomas (PCCs) and paragangliomas (PGLs).
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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