A satellite cell-specific knockout of the androgen receptor reveals myostatin as a direct androgen target in skeletal muscle

被引：93

作者：

Dubois, Vanessa ^{[1
]}

Laurent, Michal R. ^{[1
,2
]}

Sinnesael, Mieke ^{[3
]}

Cielen, Nele ^{[4
]}

Helsen, Christine ^{[1
]}

Clinckemalie, Liesbeth ^{[1
]}

Spans, Lien ^{[1
]}

Gayan-Ramirez, Ghislaine ^{[4
]}

Deldicque, Louise ^{[5
]}

Hespel, Peter ^{[5
]}

Carmeliet, Geert ^{[3
]}

Vanderschueren, Dirk ^{[3
]}

Claessens, Frank ^{[1
]}

机构：

[1] Katholieke Univ Leuven, Mol Endocrinol Lab, B-3000 Leuven, Belgium

[2] Katholieke Univ Leuven, Div Gerontol & Geriatr, B-3000 Leuven, Belgium

[3] Katholieke Univ Leuven, Div Clin & Expt Endocrinol, B-3000 Leuven, Belgium

[4] Katholieke Univ Leuven, Div Pneumol, B-3000 Leuven, Belgium

[5] Katholieke Univ Leuven, Exercise Physiol Res Grp, B-3000 Leuven, Belgium

来源：

FASEB JOURNAL | 2014年 / 28卷 / 07期

关键词：

mouse model; fiber type; microarray; DNA response element; hormone response element; GROWTH-FACTOR; BODY-COMPOSITION; MALE-MICE; MYOGENIC DIFFERENTIATION; SIGNALING PATHWAYS; RAT MODEL; TESTOSTERONE; EXPRESSION; STRENGTH; MASS;

D O I：

10.1096/fj.14-249748

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：2979 / 2994

页数：16