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Glucocorticoid receptor signaling is required for acclimation of skeletal muscle to hypobaric hypoxia

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dc.contributor.authorWhitcomb, Luke, author
dc.contributor.authorChicco, Adam, advisor
dc.contributor.authorMaresh, Ryan, advisor
dc.contributor.authorMelby, Christopher, committee member
dc.date.accessioned2022-05-30T10:21:23Z
dc.date.available2024-05-24T10:21:23Z
dc.date.issued2022
dc.description.abstractHypobaric hypoxia (HH) encountered at high altitudes acutely impairs aerobic exercise capacity, which partially recovers following 1-2 weeks of acclimation to chronic HH. Persistent elevations in serum glucocorticoids occur during HH exposure, but their role in these acute and chronic physiological responses is unclear. We tested the hypothesis that glucocorticoid signaling is essential for the acclimation of aerobic exercise capacity to chronic HH, in part by mediating adaptive changes in skeletal muscle metabolism. Male F344 rats were administered the glucocorticoid receptor antagonist RU486 (RU; 60 mg/kg/d in chow) or no drug for 5 days prior to 15 days of continued normoxia (Fort Collins, CO; elevation 5,003 feet) or HH (simulated 17,200 feet in a hypobaric chamber) with or without continuous RU treatment (N=4-8/group). Graded treadmill exercise tests (GXT) were conducted on a motorized treadmill in normoxia, during acute HH exposure, and in HH after 15 days of HH acclimation. As expected, acute HH reduced GXT performance compared to normoxia in all rats, which improved following 15 days of acclimation to HH. RU pretreatment did not impact hypoxic GXT performance, but continuous treatment abolished improvements in GXT performance following chronic HH. RU attenuated HH-induced increases in hematocrit and muscle fatty acid oxidation efficiency assessed by high-resolution respirometry ex vivo, suggesting that glucocorticoid signaling may improve muscle oxygen utilization in response to chronic HH. RU also prevented HH-induced decreases in pyruvate dehydrogenase expression and increases in Krüppel-like factor 15, proteolysis and branched-chain amino acid aminotransferase in glycolytic muscle, implicating glucocorticoid signaling in a rewiring of glucose and protein catabolism to rid the cell of excess nitrogen in HH. In conclusion, these results demonstrate that glucocorticoid receptor signaling is essential for the acclimation of aerobic exercise capacity to HH, perhaps by mediating improvements in the bioenergetic efficiency of skeletal muscle metabolism.
dc.format.mediumborn digital
dc.format.mediummasters theses
dc.identifierWhitcomb_colostate_0053N_17116.pdf
dc.identifier.urihttps://hdl.handle.net/10217/235201
dc.languageEnglish
dc.language.isoeng
dc.publisherColorado State University. Libraries
dc.relation.ispartof2020-
dc.rightsCopyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright.
dc.subjecthigh altitude
dc.subjectmitochondria
dc.subjectskeletal muscle
dc.subjecthypobaric hypoxia
dc.subjectfiber type
dc.subjectproteolysis
dc.titleGlucocorticoid receptor signaling is required for acclimation of skeletal muscle to hypobaric hypoxia
dc.typeText
dcterms.embargo.expires2024-05-24
dcterms.embargo.terms2024-05-24
dcterms.rights.dplaThis Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).
thesis.degree.disciplineBiomedical Sciences
thesis.degree.grantorColorado State University
thesis.degree.levelMasters
thesis.degree.nameMaster of Science (M.S.)

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