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A satellite cell-specific knockout of the androgen receptor reveals myostatin as a direct androgen target in skeletal muscle.
- Source :
- FASEB Journal; Jul2014, Vol. 28 Issue 7, p2979-2994, 16p
- Publication Year :
- 2014
-
Abstract
- 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 ~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 (-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. [ABSTRACT FROM AUTHOR]
- Subjects :
- MUSCLES
ANDROGENS
SATELLITE cells
CYTOLOGICAL research
ANDROSTANE
Subjects
Details
- Language :
- English
- ISSN :
- 08926638
- Volume :
- 28
- Issue :
- 7
- Database :
- Complementary Index
- Journal :
- FASEB Journal
- Publication Type :
- Academic Journal
- Accession number :
- 96991564
- Full Text :
- https://doi.org/10.1096/fj.14-249748