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Here, we studied the impact of estrogen depletion (via ovariectomy) on exercise tolerance and muscle mitochondrial metabolism in female\n                    <jats:italic>mdx<\/jats:italic>\n                    mice and the potential of estrogen replacement therapy (using estradiol) to protect against functional and metabolic perturbations. We also investigated the effect of estrogen depletion, and replacement, on the skeletal muscle proteome through an untargeted proteomic approach with TMT\u2010labelling. Our study confirms that loss of estrogen in female\n                    <jats:italic>mdx<\/jats:italic>\n                    mice reduces exercise capacity, tricarboxylic acid cycle intermediates, and citrate synthase activity but that these deficits are offset through estrogen replacement therapy. Furthermore, ovariectomy downregulated protein expression of RNA\u2010binding motif factor 20 (Rbm20), a critical regulator of sarcomeric and muscle homeostasis gene splicing, which impacted pathways involving ribosomal and mitochondrial translation. Estrogen replacement modulated Rbm20 protein expression and promoted metabolic processes and the upregulation of proteins involved in mitochondrial dynamics and metabolism. Our data suggest that estrogen mitigates dystrophinopathic features in female\n                    <jats:italic>mdx<\/jats:italic>\n                    mice and that estrogen replacement may be a potential therapy for post\u2010menopausal DMD carriers.\n                  <\/jats:p>","DOI":"10.1096\/fj.202400329r","type":"journal-article","created":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T08:44:09Z","timestamp":1717749849000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Loss of endogenous estrogen alters mitochondrial metabolism and muscle clock\u2010related protein Rbm20 in female\n                    <i>mdx<\/i>\n                    mice"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4567-4319","authenticated-orcid":false,"given":"Cara A.","family":"Timpani","sequence":"first","affiliation":[{"name":"Institute for Health and Sport (IHeS) Victoria University  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