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J Appl Physiol (January 11, 2007). doi:10.1152/japplphysiol.01305.2006
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Submitted on November 17, 2006
Accepted on January 3, 2007

Estradiol replacement reverses ovariectomy-induced muscle contractile and myosin dysfunction in mature female mice

Amy L. Moran1, Steven A. Nelson2, Rachel M. Landisch2, Gordon L. Warren3, and Dawn A. Lowe2*

1 Kinesiology, University of Minnesota, Minneapolis, Minnesota, United States
2 Program in Physical Therapy, University of Minnesota, Minneapolis, Minnesota, United States
3 Physical Therapy, Georgia State University, Atlanta, Georgia, United States

* To whom correspondence should be addressed. E-mail: dl{at}ddt.biochem.umn.edu.

Skeletal muscle contractility and myosin function decline following ovariectomy in mature, female mice. In the present study we tested the hypothesis that estradiol-replacement can reverse those declines. Four month-old female C57BL/6 mice (n=69) were ovariectomized (OVX) or sham-operated (Sham). Some mice were treated immediately with placebo or 17{beta}-estradiol (OVX+E2) while other mice were treated 30 days post-surgery. Thirty or sixty days post-surgery, soleus muscles were assessed in vitro for contractile function and susceptibility to eccentric contraction-induced injury. Myosin structural dynamics was analyzed in extensor digitorum longus (EDL)muscles by electron paramagnetic resonance spectroscopy. Maximal isometric tetanic force was affected by estradiol status (P<0.001) being ~10% less in soleus muscles from OVX compared with Sham mice [168 mN (SD 16.7) vs. 180 mN (SD 14.4)] and was restored in OVX+E2 mice [187 mN (SD 17.6)]. The fraction of strong-binding myosin during contraction was also affected (P=0.045) and was ~15% lower in EDL muscles from OVX compared with OVX+E2 mice [0.263 (SD 0.034) vs. 0.311 (SD 0.022)]. Plasma estradiol levels were correlated with Po (r=0.458; P<0.001) and active stiffness (r=0.329; P=0.044) indicating that circulating estradiol influenced muscle and myosin function. Estradiol was not effective in protecting muscle against an acute eccentric contraction-induced injury (P≥0.401) but did restore ovariectomy-induced increases in muscle wet mass caused by fluid accumulation. Collectively, estradiol had a beneficial effect on female mouse skeletal muscle.




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