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1 Molecular, Cellular, and Integrative Physiology Graduate Group, University of California, Davis, CA, USA
2 Physical Therapy Program, University of Missouri, Columbia, MO, USA
3 Physical Therapy Program, University of Missouri, Columbia, MO, USA; Center for Gender Physiology, University of Missouri, Columbia, MO, USA; Biomedical Sciences, University of Missouri, Columbia, MO, USA
4 Section of Neurobiology, Physiology, and Behavior, University of California, Davis, CA, USA; Department of Physiology and Membrane Biology, University of California, Davis, CA, USA
* To whom correspondence should be addressed. E-mail: eespangenburg{at}ucdavis.edu.
The recovery of atrophied muscle mass in animals is thought to be dependent upon on a number of factors including hormones, cytokines, and/or growth factor expression. The Akt/mTOR signaling pathway is believed to be activated by these various factors resulting in skeletal muscle growth through the initiation of protein synthesis. It was hypothesized that surgical removal of the ovaries (OVX) may alter activation of the Akt/mTOR signaling pathway, a mechanism necessary for muscle regrowth. To test this, thirty six Sprague-Dawley rats underwent OVX or sham surgeries. A portion of the animals were then subjected to hindlimb unloading (HLU) for 28 days. Following HLU, one group of sham and OVX rats underwent a 14 day recovery period where the animals were allowed free cage ambulation. The HLU animals demonstrated ~21-27% reduction in medial gastrocnemius muscle mass irrespective of whether the ovaries were intact or not. The sham animals that were re-loaded recovered their atrophied muscle mass, however the OVX group failed to recover any of the atrophied muscle mass with reloading. The failure to recover muscle mass in the OVX group was associated with reduced phosphorylation levels of both Akt and p70s6k, while in the Sham recovery animals no reductions were found in Akt phosphorylation and significant increases in p70s6k activation were detected. Finally, no differences were detected in mTOR phosphorylation in any of Sham or OVX groups. These results suggest that ovariectomy surgeries could be detrimental to the recovery of atrophied muscle mass.
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