Estradiol replacement reverses ovariectomy-induced muscle contractile and myosin dysfunction in mature female mice
Estradiol replacement reverses ovariectomy-induced muscle contractile and myosin dysfunction in mature female mice
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DOI：
10.1152/japplphysiol.01305.2006
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发表时间：
2007-04-01
影响因子：
3.3
通讯作者：
Lowe, Dawn A.
中科院分区：
文献类型：
--
作者：
Moran, Amy L.;Nelson, Steven A.;Lowe, Dawn A.
成熟雌性小鼠卵巢切除术后肌肉收缩力和肌球蛋白功能下降。在本研究中，我们验证了雌二醇替代可以逆转这些下降的假设。将四岁雌性C57 BL/6小鼠（n = 69）进行卵巢切除（OVX）或假手术。一些小鼠立即用安慰剂或17 β-雌二醇（OVX + E-2）治疗，而其他小鼠在手术后30天治疗。术后30或60天，在体外评估比目鱼肌的收缩功能和对。离心性收缩引起的损伤应用电子顺磁共振波谱分析了趾长伸肌肌球蛋白的结构动力学。最大等长强直力受雌二醇状态的影响（P < 0.001），与假手术小鼠相比，OVX小鼠比目鱼肌中的最大等长强直力降低了10%[168 mN（SD 16.7）vs. 180 mN（SD 14.4）]，OVX + E2小鼠中的最大等长强直力恢复[187 mN（SD 17.6）]。收缩期间强结合肌球蛋白的分数也受到影响（P = 0.045），与OVX + E-2小鼠相比，OVX小鼠的EDL肌肉中强结合肌球蛋白的分数降低了15%[0.263（SD 0.034）vs. 0.311（SD 0.022）]。血浆雌二醇水平与最大等长强直力（r = 0.458; P < 0.001）和主动刚度（r = 0.329; P = 0.044）相关，表明循环雌二醇影响肌肉和肌球蛋白功能。雌二醇不能有效地保护肌肉免受急性离心收缩引起的损伤（P >= 0.401），但可以恢复卵巢切除术引起的由液体积聚引起的肌肉湿质量增加。总的来说，雌二醇对雌性小鼠骨骼肌有有益的影响。
Skeletat 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-rnonth-old female C57BL/6 mice (n = 69) were ovariectomized (OVX) or sham operated. Some mice were treated immediately with placebo or 17 beta-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 similar to 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 similar to 15% lower in EDL muscle 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 >= 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.