Title: A satellite cell-specific knockout of the androgen receptor reveals myostatin as a direct androgen target in skeletal muscle
Authors: Dubois, Vanessa ×
Laurent, Michaƫl
Sinnesael, Mieke
Cielen, Nele
Helsen, Christine
Clinckemalie, Liesbeth
Spans, Lien
Gayan-Ramirez, Ghislaine
Deldicque, Louise
Hespel, Peter
Carmeliet, Geert
Vanderschueren, Dirk
Claessens, Frank #
Issue Date: Jul-2014
Publisher: The Federation of American Societies for Experimental Biology
Series Title: FASEB Journal vol:28 issue:7 pages:2979-2994
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.-Dubois, V., Laurent, M. R., Sinnesael, M., Cielen, N., Helsen, C., Clinckemalie, L., Spans, L., Gayan-Ramirez, G., Deldicque, L., Hespel, P., Carmeliet, G., Vanderschueren, D., and Claessens, F. A satellite cell-specific knockout of the androgen receptor reveals myostatin as a direct androgen target in skeletal muscle.
ISSN: 0892-6638
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Clinical and Experimental Endocrinology
Gerontology and Geriatrics
Laboratory of Molecular Endocrinology
× corresponding author
# (joint) last author

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