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....

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Published in:Proceedings of the National Academy of Sciences - PNAS 2010-08, Vol.107 (32), p.14327-14332
Main Authors: Chambon, Céline, Duteil, Delphine, Vignaud, Alban, Ferry, Arnaud, Messaddeq, Nadia, Malivindi, Rocco, Kato, Shigeaki, Chambon, Pierre, Metzger, Daniel
Format: Article
Language:English
Subjects:
Androgen receptors
Androgen-Insensitivity Syndrome - physiopathology
Androgens
Androgens - pharmacology
Animals
Artificial satellites
Biological Sciences
Effects
Extremities - physiology
Fatigue
Hypertrophy
Insulin-like growth factors
Legs
Life Sciences
Male
Mice
Muscle Cells - chemistry
Muscle Development
Muscle Strength
Muscle, Skeletal - physiology
Muscles
Musculoskeletal system
Receptors, Androgen - physiology
Rodents
Sarcomeres
Skeletal muscle
Testosterone
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1009536107