The androgen receptor in mesenchymal progenitors regulates skeletal muscle mass via Igf1 expression in male mice
成果类型：
Article
署名作者：
Sakai, Hiroshi; Uno, Hideaki; Yamakawa, Harumi; Tanaka, Kaori; Ikedo, Aoi; Uezumi, Akiyoshi; Ohkawa, Yasuyuki; Imai, Yuuki
署名单位：
Ehime University; Ehime University; Kyushu University; Kyushu University
刊物名称：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN/ISSBN：
0027-12553
DOI：
10.1073/pnas.2407768121
发表日期：
2024-09-24
关键词：
insulin sensitivity
body-composition
satellite cells
testosterone
strength
regeneration
distinct
lineage
men
bulbocavernosus
摘要：
Androgens exert their effects primarily by binding to the androgen receptor (AR), ligand- dependent nuclear receptor. While androgens have anabolic effects on skeletal muscle, previous studies reported that AR functions in myofibers to regulate skeletal muscle quality, rather than skeletal muscle mass. Therefore, the anabolic effects of androgens are exerted via nonmyofiber cells. In this context, the cellular and molecular mechanisms of AR in mesenchymal progenitors, which play a crucial role in maintaining skeletal muscle homeostasis, remain largely unknown. In this study, we demonstrated expression of AR in mesenchymal progenitors and found that targeted AR ablation in mesenchymal progenitors reduced limb muscle mass in mature adult, but not young or aged, male mice, although fatty infiltration of muscle was not affected. The absence of AR in mesenchymal progenitors led to remarkable perineal muscle hypotrophy, regardless of age, due to abnormal regulation of transcripts associated with cell death and extracellular matrix organization. Additionally, we revealed that AR in mesenchymal progenitors regulates the expression of insulin- like growth factor 1 (Igf1) and that IGF1 administration prevents perineal muscle atrophy in a paracrine manner. These findings indicate that the anabolic effects of androgens regulate skeletal muscle mass via, at least in part, AR signaling in mesenchymal progenitors.