Intermittent glucocorticoid treatment enhances skeletal muscle performance through sexually dimorphic mechanisms
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 sexu...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Clinical Investigation
2022-03-01
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| Series: | The Journal of Clinical Investigation |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/JCI149828 |
| _version_ | 1811329333756690432 |
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| author | Isabella M. Salamone Mattia Quattrocelli David Y. Barefield Patrick G. Page Ibrahim Tahtah Michele Hadhazy Garima Tomar Elizabeth M. McNally |
| author_facet | Isabella M. Salamone Mattia Quattrocelli David Y. Barefield Patrick G. Page Ibrahim Tahtah Michele Hadhazy Garima Tomar Elizabeth M. McNally |
| author_sort | Isabella M. Salamone |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T15:42:03Z |
| format | Article |
| id | doaj.art-4f9ec8dcc4bb4c1e9ae34469113326fe |
| institution | Directory Open Access Journal |
| issn | 1558-8238 |
| language | English |
| last_indexed | 2024-04-13T15:42:03Z |
| publishDate | 2022-03-01 |
| publisher | American Society for Clinical Investigation |
| record_format | Article |
| series | The Journal of Clinical Investigation |
| spelling | doaj.art-4f9ec8dcc4bb4c1e9ae34469113326fe2022-12-22T02:41:08ZengAmerican Society for Clinical InvestigationThe Journal of Clinical Investigation1558-82382022-03-011326Intermittent glucocorticoid treatment enhances skeletal muscle performance through sexually dimorphic mechanismsIsabella M. SalamoneMattia QuattrocelliDavid Y. BarefieldPatrick G. PageIbrahim TahtahMichele HadhazyGarima TomarElizabeth M. McNallyGlucocorticoid 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.https://doi.org/10.1172/JCI149828EndocrinologyMuscle biology |
| spellingShingle | Isabella M. Salamone Mattia Quattrocelli David Y. Barefield Patrick G. Page Ibrahim Tahtah Michele Hadhazy Garima Tomar Elizabeth M. McNally Intermittent glucocorticoid treatment enhances skeletal muscle performance through sexually dimorphic mechanisms The Journal of Clinical Investigation Endocrinology Muscle biology |
| title | Intermittent glucocorticoid treatment enhances skeletal muscle performance through sexually dimorphic mechanisms |
| title_full | Intermittent glucocorticoid treatment enhances skeletal muscle performance through sexually dimorphic mechanisms |
| title_fullStr | Intermittent glucocorticoid treatment enhances skeletal muscle performance through sexually dimorphic mechanisms |
| title_full_unstemmed | Intermittent glucocorticoid treatment enhances skeletal muscle performance through sexually dimorphic mechanisms |
| title_short | Intermittent glucocorticoid treatment enhances skeletal muscle performance through sexually dimorphic mechanisms |
| title_sort | intermittent glucocorticoid treatment enhances skeletal muscle performance through sexually dimorphic mechanisms |
| topic | Endocrinology Muscle biology |
| url | https://doi.org/10.1172/JCI149828 |
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