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Sexually dimorphic mechanisms of skeletal muscle adaptation

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Skeletal muscle is a highly sexually dimorphic tissue, with males and females exhibiting differences in muscle size, gene transcription, and metabolism. This thesis describes two models wherein males and females responded to an intervention with the same physiological adaptation but through two distinct mechanisms. In the first model, mice of both sexes treated with glucocorticoid steroids once a week for a month had significantly increased skeletal muscle specific force and ATP concentration. In males, this response was the result of improvements in calcium handling and protein synthesis, while in females it was the result of changes in lipid metabolism. The second model examined patients with peripheral artery disease who were responsive or non-responsive to exercise intervention. Male responders were distinguished from non-responders by decreased expression of extracellular matrix and vasculature genes; female responders had increased expression of mitochondrial genes compared to non-responsive females. Lipid metabolism was a major feature of the skeletal muscle response of females in both models, suggesting that female skeletal muscle may leverage changes in oxidative metabolism to make beneficial adaptations. Overall, this work demonstrates the critical importance of investigating both sexes when determining the mechanism of action behind skeletal muscle adaptations to ergogenic stimuli.

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