Androgen receptor coordinates muscle metabolic and contractile functions

Autor: Kamar Ghaibour, Mélanie Schuh, Sirine Souali‐Crespo, Céline Chambon, Anouk Charlot, Joe Rizk, Daniela Rovito, Anna‐Isavella Rerra, Qingshuang Cai, Nadia Messaddeq, Joffrey Zoll, Delphine Duteil, Daniel Metzger
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Journal of Cachexia, Sarcopenia and Muscle, Vol 14, Iss 4, Pp 1707-1720 (2023)
Druh dokumentu: article
ISSN: 2190-6009
2190-5991
DOI: 10.1002/jcsm.13251
Popis: Abstract Background Androgens are anabolic steroid hormones that exert their function by binding to the androgen receptor (AR). We have previously established that AR deficiency in limb muscles impairs sarcomere myofibrillar organization and decreases muscle strength in male mice. However, despite numerous studies performed in men and rodents, the signalling pathways controlled by androgens via their receptor in skeletal muscles remain poorly understood. Methods Male ARskm−/y (n = 7–12) and female ARskm−/− mice (n = 9), in which AR is selectively ablated in myofibres of musculoskeletal tissue, and male AR(i)skm−/y, in which AR is selectively ablated in post‐mitotic skeletal muscle myofibres (n = 6), were generated. Longitudinal monitoring of body weight, blood glucose, insulin, lipids and lipoproteins was performed, alongside metabolomic analyses. Glucose metabolism was evaluated in C2C12 cells treated with 5α‐dihydrotestosterone (DHT) and the anti‐androgen flutamide (n = 6). Histological analyses on macroscopic and ultrastructural levels of longitudinal and transversal muscle sections were conducted. The transcriptome of gastrocnemius muscles from control and ARskm−/y mice was analysed at the age of 9 weeks (P
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