Intermittent glucocorticoid treatment enhances skeletal muscle performance through sexually dimorphic mechanisms
Year: 2022
Type: article
Abstract: Glucocorticoid steroids are commonly prescribed for many inflammatory conditions, but chronic daily use produces adverse effects, including muscle wasting and weakness. In contrast, shorter glucocorticoid pulses may improve athletic performance, although the mechanisms remain unclear. Muscle is sexually dimorphic and comparatively little is known about how male and female muscles respond to glucocorticoids. We investigated the impact of once-weekly glucocorticoid exposure on skeletal muscle performance comparing male and female mice. One month of once-weekly glucocorticoid dosing improved muscle specific force in both males and females. Transcriptomic profiling of isolated myofibers identified a striking sexually dimorphic response to weekly glucocorticoids. Male myofibers had increased expression of genes in the IGF1/PI3K pathway and calcium handling, while female myofibers had profound upregulation of lipid metabolism genes. Muscles from weekly prednisone-treated males had improved calcium handling, while comparably treated female muscles had reduced intramuscular triglycerides. Consistent with altered lipid metabolism, weekly prednisone-treated female mice had greater endurance relative to controls. Using chromatin immunoprecipitation, we defined a sexually dimorphic chromatin landscape after weekly prednisone. These results demonstrate that weekly glucocorticoid exposure elicits distinct pathways in males versus females, resulting in enhanced performance.
DOI: 10.1172/jci149828
Authors: Isabella M. Salamone, Mattia Quattrocelli, David Y. Barefield, Patrick G. Page, Ibrahim Tahtah, Michele Hadhazy, Garima Tomar, Elizabeth M. McNally
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,200
Funders: Foundation for the National Institutes of Health, Northwestern University, University of Virginia, National Institutes of Health, University of Illinois at Urbana-Champaign, University of Illinois at Chicago, National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Institute of Arthritis and Musculoskeletal and Skin Diseases
Awards: FAILED REGENERATION IN THE MUSCULAR DYSTROPHIES: INFLAMMATION, FIBROSIS AND FAT, Myofilament proteins in cardiomyopathy and arrhythmias, CHRONO-MECHANISMS of CARDIOMETABOLIC PHARMACOLOGY, Dose-specific responsiveness of glucocorticoid receptor-driven transcription in skeletal muscle, Understanding and Improving Therapies for the Muscular Dystrophies, G5459344496, G5506992838, G55336246, Myofilament proteins in cardiomyopathy and arrhythmias, G6471144788, Glucocorticoid and circadian clock coregulation of insulin sensitivity and metabolism, G6801128911, G7478307010, Sarcoglycan in Myopathy and Muscle Membrane Stability, G8556152910, G9000069142, Mechanisms of resealing and rebuilding in muscle repair, NW University Program in Endo Diabetes and Hormone Action
OpenAlex ID: W4211147224