| Autor: |
Onishi T; Department of Urology, Ehime University Graduate School of Medicine, Ehime 791-0295, Japan., Sakai H; Division of Integrative Pathophysiology, Proteo-Science Center, Ehime University, Ehime 791-0295, Japan.; Department of Pathophysiology, Ehime University Graduate School of Medicine, Ehime 791-0295, Japan., Uno H; Department of Pathophysiology, Ehime University Graduate School of Medicine, Ehime 791-0295, Japan., Sakakibara I; Department of Physiology, School of Medicine, Aichi Medical University, Aichi 480-1195, Japan., Uezumi A; Division of Cell Heterogeneity, Medical Research Center for High Depth Omics, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan., Honda M; Pharmaceuticals and Life Sciences Division, Shimadzu Techno-Research, Inc., Kyoto 604-8436, Japan., Kai T; Pharmaceuticals and Life Sciences Division, Shimadzu Techno-Research, Inc., Kyoto 604-8436, Japan., Higashiyama S; Department of Cell Growth and Tumor Regulation, Proteo-Science Center, Ehime University, Ehime 791-0295, Japan.; Department of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime 791-0295, Japan.; Department of Oncogenesis and Growth Regulation, Research Institute, Osaka International Cancer Institute, Osaka 541-8567, Japan., Miura N; Department of Urology, Ehime University Graduate School of Medicine, Ehime 791-0295, Japan., Kikugawa T; Department of Urology, Ehime University Graduate School of Medicine, Ehime 791-0295, Japan., Saika T; Department of Urology, Ehime University Graduate School of Medicine, Ehime 791-0295, Japan., Imai Y; Division of Integrative Pathophysiology, Proteo-Science Center, Ehime University, Ehime 791-0295, Japan.; Department of Pathophysiology, Ehime University Graduate School of Medicine, Ehime 791-0295, Japan. |
| Abstrakt: |
Androgen is widely acknowledged to regulate skeletal muscle mass. However, the specific mechanism driving muscle atrophy resulting from androgen deficiency remains elusive. Systemic androgen receptor knockout (ARKO) mice exhibit reduction in both muscle strength and muscle mass while skeletal muscle fiber specific ARKO mice have decreased muscle strength without affecting skeletal muscle mass in the limbs. Therefore, androgens may indirectly regulate skeletal muscle mass through effects on non-myofibers. Considering this, our investigation focused on blood fluid factors that might play a role in the regulation of skeletal muscle mass under the influence of androgens. Using a male mouse model of sham, orchidectomy and DHT replacement, mass spectrometry for serum samples of each group identified epidermal growth factor receptor (EGFR) as a candidate protein involving the regulation of skeletal muscle mass affected by androgens. Egfr expression in both liver and epididymal white adipose tissue correlated with androgen levels. Furthermore, Egfr expression in these tissues was predominantly elevated in male compared to female mice. Interestingly, male mice exhibited significantly elevated serum EGFR concentrations compared to their female counterparts, suggesting a connection with androgen levels. Treatment of EGFR to C2C12 cells promoted phosphorylation of AKT and its downstream S6K, and enhanced the protein synthesis in vitro. Furthermore, the administration of EGFR to female mice revealed a potential role in promoting an increase in skeletal muscle mass. These findings collectively enhance our understanding of the complex interplay among androgens, EGFR, and the regulation of skeletal muscle mass. |
