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Ovariectomy prevents the recovery of atrophied gastrocnemius skeletal muscle mass

¹Molecular, Cellular, and Integrative Physiology Graduate Group, University of California Davis; ²Physical Therapy Program, ³Center for Gender Physiology, and ⁴Biomedical Sciences, University of Missouri, Columbia, Missouri; ⁵Section of Neurobiology, Physiology, and Behavior, Division of Biological Sciences, and ⁶Department of Physiology and Membrane Biology, School of Medicine, University of California, Davis, California

Submitted 18 July 2005 ; accepted in final form 6 September 2005

The recovery of atrophied muscle mass in animals is thought to be dependent on a number of factors including hormones, cytokines, and/or growth factor expression. The Akt/mammalian target of rapamycin (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, 36 Sprague-Dawley rats underwent Ovx or sham surgeries. A portion of the animals were then subjected to hindlimb unloading (HLU) for 28 days. After HLU, one group of Sham and Ovx rats underwent a 14-day recovery period in which 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 reloaded 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 p70^s6k, whereas in the Sham recovery animals no reductions were found in Akt phosphorylation and significant increases in p70^s6k 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.

estrogens; mammalian target of rapamycin; p70^s6k; protein synthesis

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