Estrogens are female sex hormones that are important for comprehensively maintaining muscle function, and an insufficiency affects muscle strength and regeneration in females. However, it is still unclear whether estrogen signaling is mediated through receptors. To investigate the specific role of estrogen receptor β (ERβ) in skeletal muscle and satellite cells (muscle stem cells), we generated muscle-specific ERβ-knockout (mKO) and satellite cell-specific ERβ-knockout (scKO) mice, respectively. Young female mKO mice displayed a decrease in fast-type dominant muscle mass. Female, but not male, scKO mice exhibited impaired muscle regeneration following acute muscle injury, probably due to reduced proliferation and increased apoptosis of satellite cells. RNA-sequencing analysis revealed that loss of ERβ in satellite cells altered gene expression of extracellular matrix components, including laminin and collagen. The results indicate that the estrogen-ERβ pathway is a sex-specific regulatory mechanism that controls muscle growth and regeneration in female mice.

雌激素是女性性激素，对于全面维持肌肉功能非常重要，功能不足会影响女性的肌肉力量和再生。然而，还不清楚雌激素信号传导是否通过受体介导。为了研究雌激素受体β（ERβ）在骨骼肌和卫星细胞（肌肉干细胞）中的特定作用，我们分别生成了肌肉特异性ERβ基因敲除（mKO）和卫星细胞特异性ERβ基因敲除（scKO）小鼠。年轻的雌性mKO小鼠表现出快速型优势肌质量下降。雌性而不是雄性的scKO小鼠在急性肌肉损伤后表现出受损的肌肉再生能力，这可能是由于卫星细胞的增殖减少和凋亡增加所致。RNA测序分析表明，卫星细胞中ERβ的丢失改变了细胞外基质成分（包括层粘连蛋白和胶原蛋白）的基因表达。结果表明，雌激素-ERβ途径是一种性别特异性调节机制，可控制雌性小鼠的肌肉生长和再生。