Résumé :
|
Skeletal muscles play an important role in stature, respiration and locomotion, and serve as the most significant repository for proteins in the body. Fasting, various diseases and ageing induce muscle atrophy and weakness that is often severely disabilitating, can lead to physical dependence, and therefore has a high socio-economical impact. Glucocorticoids (GC) are widely used for the treatment of inflammatory and auto-immune disorders, but a prolonged therapy is limited due to muscle wasting. In contrast, androgens exert anabolic effects on skeletal muscle, but their use is limited as they promote prostate cancer. Most of the effects of these hormones are transduced by two members of the nuclear receptor superfamily, the androgen and GC receptors (AR and GR, respectively). As the molecular and cellular pathways controlled by these hormones in skeletal muscle remain poorly understood, we generated mice in which AR and GR are selectively ablated in skeletal muscle myofibers. Our results show that myofiber GR negatively regulates limb muscle mass through anti-anabolic and catabolic activities, while AR is essential for maximal force production in limb skeletal muscles by controlling the integrity of the myofibrillar organisation of sarcomeres. The identification of the molecular mechanisms controlled by these two steroid hormones in skeletal muscles might allow to design new screens to improve their tissue selectivity for clinical use, and identify new drug target to combat muscle wasting.
|