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J Appl Physiol 102: 1387-1393, 2007. First published January 11, 2007; doi:10.1152/japplphysiol.01305.2006
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Estradiol replacement reverses ovariectomy-induced muscle contractile and myosin dysfunction in mature female mice

Amy L. Moran,1 Steven A. Nelson,2 Rachel M. Landisch,2 Gordon L. Warren,3 and Dawn A. Lowe2

1School of Kinesiology and 2Department of Physical Medicine and Rehabilitation, University of Minnesota, Minneapolis, Minnesota; and 3Division of Physical Therapy, Georgia State University, Atlanta, Georgia

Submitted 17 November 2006 ; accepted in final form 3 January 2007

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. Some mice were treated immediately with placebo or 17beta-estradiol (OVX + E2) while other mice were treated 30 days postsurgery. Thirty or sixty days postsurgery, 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-operated 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 maximal isometric tetanic force (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.

estrogen; skeletal muscle; muscle force; menopause; hormones



Address for reprint requests and other correspondence: D. A. Lowe, Dept. of Physical Medicine and Rehabilitation, Univ. of Minnesota, MMC 388, 420 Delaware St. SE, Minneapolis, MN 55455 (e-mail: lowex017{at}umn.edu)




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