title: A satellite cell-specific knockout of the androgen receptor reveals myostatin as a direct androgen target in skeletal muscle.
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.
authors.affiliation: Molecular Endocrinology Laboratory.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Dubois
authors.affiliation: Molecular Endocrinology Laboratory, Division of Gerontology and Geriatrics.
authors.forename: Michaël R
authors.initials: MR
authors.lastname: Laurent
authors.affiliation: Division of Clinical and Experimental Endocrinology.
authors.forename: Mieke
authors.initials: M
authors.lastname: Sinnesael
authors.affiliation: Division of Pneumology, and.
authors.forename: Nele
authors.initials: N
authors.lastname: Cielen
authors.affiliation: Molecular Endocrinology Laboratory.
authors.forename: Christine
authors.initials: C
authors.lastname: Helsen
authors.affiliation: Molecular Endocrinology Laboratory.
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Clinckemalie
authors.affiliation: Molecular Endocrinology Laboratory.
authors.forename: Lien
authors.initials: L
authors.lastname: Spans
authors.affiliation: Division of Pneumology, and.
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Gayan-Ramirez
authors.affiliation: Exercise Physiology Research Group, KU Leuven, Campus Gasthuisberg, Leuven, Belgium.
authors.forename: Louise
authors.initials: L
authors.lastname: Deldicque
authors.affiliation: Exercise Physiology Research Group, KU Leuven, Campus Gasthuisberg, Leuven, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Hespel
authors.affiliation: Division of Clinical and Experimental Endocrinology.
authors.forename: Geert
authors.initials: G
authors.lastname: Carmeliet
authors.affiliation: Division of Clinical and Experimental Endocrinology.
authors.forename: Dirk
authors.initials: D
authors.lastname: Vanderschueren
authors.affiliation: Molecular Endocrinology Laboratory, frank.claessens@med.kuleuven.be.
authors.forename: Frank
authors.initials: F
authors.lastname: Claessens
mesh_terms: D000728:Androgens / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D005121:Extremities; D005260:Female; D015870:Gene Expression / Q000235:genetics; D006984:Hypertrophy / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D053580:Muscle Strength / Q000235:genetics; D009135:Muscular Diseases / Q000235:genetics / Q000378:metabolism; D032446:Myoblasts / Q000378:metabolism; D055435:Myostatin / Q000235:genetics / Q000378:metabolism*; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism*; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: D000728:Androgens; C525912:Mstn protein, mouse; D055435:Myostatin; D011944:Receptors, Androgen
keywords: DNA response element; fiber type; hormone response element; microarray; mouse model