Kitajima Yuriko, Ono Yusuke
Department of Stem Cell BiologyAtomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Department of Stem Cell BiologyAtomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
J Endocrinol. 2016 Jun;229(3):267-75. doi: 10.1530/JOE-15-0476. Epub 2016 Apr 5.
Estrogens have crucial roles in an extensive range of physiological functions regulating cellular proliferation and differentiation, development, homeostasis, and metabolism. Therefore, prolonged estrogen insufficiency influences various types of tissues expressing estrogen receptors (ERs). Although ERs are expressed in skeletal muscle and its stem cells, called satellite cells, how prolonged estrogen insufficiency affects their function remains unclear. In this study, we investigated the effect of estrogen reduction on muscle in young ovariectomized (OVX) female mice. We found that reduced estrogens resulted in muscle atrophy in a time-dependent manner. Muscle force generation was reduced in OVX mice. Interestingly, prolonged estrogen insufficiency shifted fiber types toward faster myosin heavy chain isoforms. The number of satellite cells per isolated myofiber was unchanged, while satellite cell expansion, differentiation, and self-renewal were all markedly impaired in OVX mice. Indeed, muscle regeneration was significantly compromised in OVX mice. Taken together, our results demonstrate that estrogens are essential for comprehensively maintaining muscle function with its insufficiency affecting muscle strength and regeneration in young female mice.
雌激素在广泛的生理功能中发挥着关键作用，这些生理功能包括调节细胞增殖与分化、发育、体内平衡以及新陈代谢。因此，长期雌激素不足会影响各种表达雌激素受体（ERs）的组织。尽管ERs在骨骼肌及其干细胞（即卫星细胞）中表达，但长期雌激素不足如何影响它们的功能仍不清楚。在本研究中，我们调查了雌激素减少对年轻去卵巢（OVX）雌性小鼠肌肉的影响。我们发现雌激素减少会导致肌肉萎缩，且呈时间依赖性。OVX小鼠的肌肉力量产生减少。有趣的是，长期雌激素不足使纤维类型向更快的肌球蛋白重链异构体转变。每个分离的肌纤维中的卫星细胞数量没有变化，而在OVX小鼠中卫星细胞的扩增、分化和自我更新均明显受损。事实上，OVX小鼠的肌肉再生受到显著损害。综上所述，我们的结果表明，雌激素对于全面维持肌肉功能至关重要，其不足会影响年轻雌性小鼠的肌肉力量和再生。
