期刊
FASEB JOURNAL
卷 28, 期 7, 页码 2979-2994出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.14-249748
关键词
mouse model; fiber type; microarray; DNA response element; hormone response element
资金
- Flemish Fund for Scientific Research (FWO) [G.0858.11N]
- KU Leuven [OT/11/081, OT/09/035]
- FWO
Androgens have well-established anabolic actions on skeletal muscle, although the direct effects of the androgen receptor (AR) in muscle remain unclear. We generated satellite cell-specific AR-knockout (satARKO) mice in which the AR is selectively ablated in satellite cells, the muscle precursor cells. Total-limb maximal grip strength is decreased by 7% in satARKO mice, with soleus muscles containing similar to 10% more type I fibers and 10% less type IIa fibers than the corresponding control littermates. The weight of the perineal levator ani muscle is markedly reduced (similar to 52%). Thus, muscle AR is involved in fiber-type distribution and force production of the limb muscles, while it is a major determinant of the perineal muscle mass. Surprisingly, myostatin (Mstn), a strong inhibitor of skeletal muscle growth, is one of the most androgen-responsive genes (6-fold reduction in satARKO) through direct transcription activation by the AR. Consequently, muscle hypertrophy in response to androgens is augmented in Mstn-knockout mice. Our finding that androgens induce Mstn signaling to restrain their own anabolic actions has implications for the treatment of muscle wasting disorders.
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