Estrogen Receptor β Controls Muscle Growth and Regeneration in Young Female Mice

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 e...

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Bibliographic Details
Published in:Stem cell reports 2020-09, Vol.15 (3), p.577-586
Main Authors: Seko, Daiki, Fujita, Ryo, Kitajima, Yuriko, Nakamura, Kodai, Imai, Yuuki, Ono, Yusuke
Format: Article
Language:English
Subjects:
estrogen receptor β
estrogens
muscle growth
muscle mass
muscle regeneration
muscle stem cells
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Summary: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. [Display omitted] •ERβ controls muscle growth in young female mice•ERβ is essential for muscle regeneration in female mice•Inactivation of ERβ causes an increase in apoptosis•ERβ is required for satellite cell population expansion In this article, Seko et al. demonstrate that ERβ is a female-specific regulator of muscle growth and regeneration. Muscle-specific ERβ-deleted young female mice exhibited a decrease in muscle mass, while satellite cell-specific ERβ inactivation resulted in impaired muscle regeneration following acute muscle injury in female mice due to reduced proliferation and increased apoptosis of satellite cells.
ISSN:2213-6711
2213-6711
DOI:10.1016/j.stemcr.2020.07.017