title: Estradiol replacement reverses ovariectomy-induced muscle contractile and myosin dysfunction in mature female mice.
abstract: 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 + E(2)) 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 approximately 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 + E(2) mice [187 mN (SD 17.6)]. The fraction of strong-binding myosin during contraction was also affected (P = 0.045) and was approximately 15% lower in EDL muscles from OVX compared with OVX + E(2) 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 >or= 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.
authors.affiliation: School of Kinesiology, University of Minnesota, Minneapolis, Minnesota 55455, USA. lowex017@umn.edu
authors.forename: Amy L
authors.initials: AL
authors.lastname: Moran
authors.forename: Steven A
authors.initials: SA
authors.lastname: Nelson
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Landisch
authors.forename: Gordon L
authors.initials: GL
authors.lastname: Warren
authors.forename: Dawn A
authors.initials: DA
authors.lastname: Lowe
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000008:administration & dosage* / Q000097:blood; D015914:Estrogen Replacement Therapy / Q000379:methods*; D005260:Female; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D009218:Myosins / Q000378:metabolism*; D010052:Ovariectomy
chemical_list: D004958:Estradiol; D009218:Myosins