Myocytic androgen receptor controls the strength but not the mass of limb muscles.
The anabolic effects of androgens on skeletal muscles are thought to be mediated predominantly through the androgen receptor (AR), a member of the ligand-dependent nuclear receptor superfamily. However, despite numerous studies performed in men and in rodents, these effects remain poorly understood. To characterize androgen signaling in skeletal muscles, we generated mice in which the AR is selectively ablated in myofibers. We show that myocytic AR controls androgen-induced insulin-like growth factor IEa (IGF-IEa) expression in the highly androgen-sensitive perineal muscles and that it mediates androgen-stimulated postnatal hypertrophy of these muscles. In contrast, androgen-dependent postnatal hypertrophy of limb muscle fibers is independent of myocytic AR. Thus, androgens control perineal and limb muscle mass in male mice through myocytic AR-dependent and -independent pathways, respectively. Importantly, we also show that AR deficiency in limb myocytes impairs myofibrillar organization of sarcomeres and decreases muscle strength, thus demonstrating that myocytic AR controls key pathways required for maximum force production. These distinct androgen signaling pathways in perineal and limb muscles may allow the design of screens to identify selective androgen modulators of muscle strength.
Chambon
Céline
C
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique Unité Mixte de Recherche 7104, Institut National de la Santé et de la Recherche Médicale U964, Université de Strasbourg, Collège de France, 67404 Illkirch, France. chambon@igbmc.fr
Duteil
Delphine
D
Vignaud
Alban
A
Ferry
Arnaud
A
Messaddeq
Nadia
N
Malivindi
Rocco
R
Kato
Shigeaki
S
Chambon
Pierre
P
Metzger
Daniel
D
D013734:Androgen-Insensitivity Syndrome / Q000503:physiopathology; D000728:Androgens / Q000494:pharmacology; D000818:Animals; D005121:Extremities / Q000502:physiology*; D008297:Male; D051379:Mice; D032342:Muscle Cells / Q000737:chemistry*; D024510:Muscle Development; D053580:Muscle Strength; D018482:Muscle, Skeletal / Q000502:physiology*; D011944:Receptors, Androgen / Q000502:physiology*; D012518:Sarcomeres
D000728:Androgens; D011944:Receptors, Androgen