Elucidation of the mechanism of androgen regulation of skeletal muscle using integrative analysis

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K19947
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 59020:Sports sciences-related
• Research Institution: Ehime University
• Principal Investigator: Sakai Hiroshi 愛媛大学, プロテオサイエンスセンター, 助教 (00820804)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: アンドロゲン / 男性ホルモン / アンドロゲン受容体 / 骨格筋 / 筋再生 / 骨格筋幹細胞 / サテライト細胞

Outline of Final Research Achievements

The anabolic effects of androgen on skeletal muscles are thought to be mediated by androgen receptor (AR). Although multiple studies concerning the effects of AR in males have been performed, the molecular mechanisms of AR in skeletal muscles remain unclear. Here we first confirmed that satellite cells from mouse hindlimb muscles express AR. We then generated satellite cell-specific AR knockout mice using Pax7CreERT2 and ARL2/Y mice to test whether AR in satellite cells is necessary for muscle regeneration. We found that muscle regeneration was compromised in both Pax7CreERT2(Fan)/+ control mice and Pax7CreERT2(Fan)/+;ARL2/Y mice compared to ARL2/Y mice. However, Pax7CreERT2(Gaka)/+;ARL2/Y mice showed no significant differences between control and mutant muscle regeneration. These findings indicate that AR in satellite cells is not essential for muscle regeneration.

Free Research Field

スポーツ科学

Academic Significance and Societal Importance of the Research Achievements

本研究ではアンドロゲン受容体遺伝子欠損マウスを用いたin vivoモデルによりアンドロゲンと骨格筋再生ならびに骨格筋幹細胞の関係を詳細に解明した。この作用機序を解明することは、アンドロゲン補充治療の副作用を解明し、サルコペニアの予防・治療の発展と、ひいては超高齢社会における健康寿命問題を克服する一つの起点となる。