title: Myofiber androgen receptor promotes maximal mechanical overload-induced muscle hypertrophy and fiber type transition in male mice.
abstract: The first aim of this study was to examine the role of myofiber androgen receptor (AR) in male mice on muscle performance gain and remodeling-induced muscle mechanical overloading (OVL) that mimics resistance training. The response of OVL in mice in which AR is selectively ablated in myofibers (AR(skm-/y)) was compared with that of wild-type (WT) mice. In addition, we determined whether the synthetic anabolic androgen nandrolone administration affects the OVL response. We found that OVL increased absolute maximal force and fatigue resistance in both mouse genotypes (P < .05). However, the absolute maximal force increased more in AR(skm-/y) mice as compared with WT mice (+88% vs +63%) (P < .05). Muscle weight increased less in response to OVL in AR(skm-/y) mice (+54%) than in WT mice (+115%) (P < .05). The fiber number per cross-section similarly increased in both mouse genotypes after OVL (P < .05). In contrast to WT mice, the diameter of the fibers expressing myosin heavy chain (MHC)-2x decreased after OVL in AR(skm-/y) mice (P < .05). The MHC-2b to MHC-2a fiber type transition in response to OVL was reduced in AR(skm-/y) mice as compared with WT mice (P < .05). Finally, nandrolone administration during OVL did not further improve absolute maximal force and fatigue resistance and markedly alter muscle remodeling in both mouse genotypes. Together, our results indicate that myofiber AR is required for a complete response to OVL and that exogenous androgens do not increase muscle performance during intensive remodeling in male mice.
authors.affiliation: Université Pierre et Marie Curie Université Paris 06 (A.F., T.M., N.V., G.B.-B.), Sorbonne Universités, Inserm Unité 974, Centre National de la Recherche Scientifique Unité Mixte de Recherche 7215, Institut de Myologie, F-75013 Paris, France; Université Paris Descartes (A.F.), Sorbonne Paris Cité, F-75006 Paris, France; Institut de Génétique et de Biologie Moléculaire et Cellulaire (M.S., D.M.), Centre National de la Recherche Scientifique Unité Mixte de Recherche 7104, Inserm Unité 964, Université de Strasbourg, Illkirch 67404, France; and Université Pierre et Marie Curie Université Paris 06 (A.P., T.M., P.J., O.A.), Sorbonne Universités, Unité Mixte de Recherche Centre National de la Recherche Scientifique 8256, Biological Adaptation and Ageing, F-75005 Paris, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Ferry
authors.forename: Mélanie
authors.initials: M
authors.lastname: Schuh
authors.forename: Ara
authors.initials: A
authors.lastname: Parlakian
authors.forename: Takouhie
authors.initials: T
authors.lastname: Mgrditchian
authors.forename: Nicolas
authors.initials: N
authors.lastname: Valnaud
authors.forename: Pierre
authors.initials: P
authors.lastname: Joanne
authors.forename: Gillian
authors.initials: G
authors.lastname: Butler-Browne
authors.forename: Onnik
authors.initials: O
authors.lastname: Agbulut
authors.forename: Daniel
authors.initials: D
authors.lastname: Metzger
mesh_terms: D000818:Animals; D006984:Hypertrophy; D008297:Male; D008810:Mice, Inbred C57BL; D024510:Muscle Development; D018485:Muscle Fibers, Skeletal / Q000378:metabolism* / Q000473:pathology; D009277:Nandrolone; D011944:Receptors, Androgen / Q000378:metabolism*; D016474:Weight-Bearing / Q000502:physiology*
chemical_list: D011944:Receptors, Androgen; D009277:Nandrolone