PDF(Pubmed)
Abstract：
Estradiol and estrogen receptor α (ERα) have been shown to be important for the maintenance of skeletal muscle strength in females; however, little is known about the roles of estradiol and ERα in male muscle. The purpose of this study was to determine if skeletal muscle ERα is required for optimal contractility in male mice. We hypothesize that reduced ERα in skeletal muscle impairs contractility in male mice. Skeletal muscle-specific knockout (skmERαKO) male mice exhibited reduced strength across multiple muscles and several contractile parameters related to force generation and kinetics compared with wild-type littermates (skmERαWT). Isolated EDL muscle-specific isometric tetanic force, peak twitch force, peak concentric and peak eccentric forces, as well as the maximal rates of force development and relaxation were 11%-21% lower in skmERαKO compared with skmERαWT mice. In contrast, isolated soleus muscles from skmERαKO mice were not affected. In vivo peak torque of the anterior crural muscles was 20% lower in skmERαKO compared with skmERαWT mice. Muscle masses, contractile protein contents, fiber types, phosphorylation of the myosin regulatory light chain, and caffeine-elicited force did not differ between muscles of skmERαKO and skmERαWT mice, suggesting that strength deficits were not due to size, composition, or calcium release components of muscle contraction. These results indicate that in male mice, reduced skeletal muscle ERα blunts contractility to a magnitude similar to that previously reported in females; however, the mechanism may be sexually dimorphic.NEW & NOTEWORTHY We comprehensively measured in vitro and in vivo contractility of leg muscles with reduced estrogen receptor α (ERα) in male mice and reported that force generation and contraction kinetics are impaired. In contrast to findings in females, phosphorylation of myosin regulatory light chain cannot account for low force production in male skeletal muscle ERα knockout mice. These results indicate that ERα is required for optimal contractility in males and females but via sexually dimorphic means.
摘要：
雌二醇和雌激素受体α（ERα）已被证明对维持女性骨骼肌力量很重要，然而，对雌二醇和ERα在男性肌肉中的作用知之甚少。这项研究的目的是确定雄性小鼠的最佳收缩性是否需要骨骼肌ERα。我们假设骨骼肌中ERα的降低会损害雄性小鼠的收缩性。与野生型同窝动物（skmERαWT）相比，骨骼肌特异性敲除（skmERαKO）雄性小鼠在多个肌肉中的力量以及与力的产生和动力学有关的几个收缩参数均降低。孤立的EDL肌肉特异性等距强直力，峰值抽搐力，峰值同心力和峰值偏心力，与skmERαWT小鼠相比，skmERαKO的最大力发展和松弛率低11-21％。相比之下,来自skmERaKO小鼠的孤立的比目鱼肌没有受到影响。与skmERαWT小鼠相比，skmERαKO的前腿肌肉的体内峰值扭矩低20％。肌肉肿块,收缩蛋白含量，纤维类型,肌球蛋白调节轻链的磷酸化，和咖啡因引起的力量在skmERαKO和skmERαWT小鼠的肌肉之间没有差异，这表明力量不足不是由于大小，composition,或肌肉收缩的钙释放成分。这些结果表明，在雄性小鼠中，骨骼肌ERα的收缩力降低到与先前在雌性中报道的相似的程度，然而,这种机制可能是性二态的。
