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Similar deficiencies, different outcomes: succinate dehydrogenase loss in adrenal medulla vs. fibroblast cell culture models of paraganglioma.
Cancer Metab
December 2024
Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science, 200 First St. SW, Rochester, MN, 55905, USA.
Heterozygosity for loss-of-function alleles of the genes encoding the four subunits of succinate dehydrogenase (SDHA, SDHB, SDHC, SDHD), as well as the SDHAF2 assembly factor predispose affected individuals to pheochromocytoma and paraganglioma (PPGL), two rare neuroendocrine tumors that arise from neural crest-derived paraganglia. Tumorigenesis results from loss of the remaining functional SDHx gene copy, leading to a cell with no functional SDH and a defective tricarboxylic acid (TCA) cycle. It is believed that the subsequent accumulation of succinate competitively inhibits multiple dioxygenase enzymes that normally suppress hypoxic signaling and demethylate histones and DNA, ultimately leading to increased expression of genes involved in angiogenesis and cell proliferation.
View Article and Find Full Text PDFPrognosis and tumor microenvironment in pseudohypoxic pheochromocytoma/paraganglioma.
Virchows Arch
December 2024
Department of Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 1358550, Japan.
Pheochromocytoma and paraganglioma (PPGL) are rare tumors that occur in the adrenal medulla and extra-adrenal tissues, respectively. The prognosis and tumor microenvironment (TME) of pseudohypoxic PPGL as a major entity have not been fully described. Based on the clinical database of 65 patients with PPGL, we assessed the morphological features as well as the immunohistochemistry of pseudohypoxia-related proteins (SDHB and CAIX) and TME-related immune cell markers.
View Article and Find Full Text PDFHormonal Dynamics in Response to Short-Term Hypoxia Exposure: Cortisol and Prolactin Regulation as Adaptive Mechanisms.
Cureus
October 2024
Department of Sport and Exercise Medicine, Faculty of Kinesiology, University of Zagreb, Zagreb, HRV.
Background: The better availability of altitude rooms in hotels and sports centers led to increased people speculating that "over-the-weekend" hypoxia might contribute to overall psychological and physical well-being.
Purpose: This study investigates the acute stress hormone response in management professionals following short-term exposure to normobaric hypoxia, amidst the increasing use of hypoxic conditions in stress-relief programs, which lack scientific validation.
Methods: Twelve healthy male subjects, employees in management positions (mean age 34.
Adrenal epinephrine facilitates erythropoietin gene activation by hypoxia through β2 adrenergic receptor interaction with Hif-2α.
Am J Physiol Regul Integr Comp Physiol
January 2025
Institute for Integrative Physiology and Center for Systems Biology of O2 Sensing, Biological Sciences Division, University of Chicago, Chicago, Illinois, United States.
Hypobaric hypoxia (HH) occurring at high altitudes activates the sympathetic nervous system (SNS) and increases circulating erythropoietin (EPO) levels. EPO stimulates red blood cell production (erythropoiesis), enhancing oxygen transport in arterial blood to counteract hypoxemia. The present study tested the hypothesis that SNS contributes to EPO activation by HH through epinephrine (EPI) release from the adrenal medullae.
View Article and Find Full Text PDFCurrent views on the role of HIF-2α in the pathogenesis and syndromic presentation of pheochromocytoma and paraganglioma.
Best Pract Res Clin Endocrinol Metab
December 2024
Department of Medicine and Department of Molecular Oncology, King Faisal Specialist Hospital & Research Center, Riyadh 11211, Saudi Arabia. Electronic address:
Article Synopsis
- - Pathogenic variants (PVs) in the EPAS1 gene, which influences the hypoxia-inducible factor HIF-2α, are linked to about 3%-6% of pheochromocytoma and paragangliomas (PPGLs), either as standalone tumors or as part of Pacak-Zhuang Syndrome (PZS) which may include additional symptoms like polycythemia and somatostatinoma.
- - The mutations in EPAS1 allow HIF-2α to escape from degradation processes, leading to its accumulation and activation of genes that promote tumor formation, particularly in those diagnosed in their second or third decade of life, with a higher prevalence in females.
- - Research into the hyp
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