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Androgen Signaling in Myocytes Contributes to the Maintenance of Muscle Mass and Fiber Type Regulation But Not to Muscle Strength or Fatigue

Laboratory for Experimental Medicine and Endocrinology (J.O., F.C., K.D.G., A.V.B., G.V., D.V.), Department of Experimental Medicine, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium; and Research Center for Exercise and Health (K.V.P., K.D.B., P.H.), Faculty of Kinesiology and Rehabilitation Sciences, Katholieke Universiteit Leuven, 3001 Heverlee, Belgium

Address all correspondence and requests for reprints to: Dirk Vanderschueren, Laboratory for Experimental Medicine and Endocrinology, Herestraat 49 B-3000 Leuven, Belgium. E-mail: Dirk.Vanderschueren{at}uz.kuleuven.be.

Muscle frailty is considered a major cause of disability in the elderly and chronically ill. However, the exact role of androgen receptor (AR) signaling in muscle remains unclear. Therefore, a postmitotic myocyte-specific AR knockout (mARKO) mouse model was created and investigated together with a mouse model with ubiquitous AR deletion. Muscles from mARKO mice displayed a marked reduction in AR protein (60–88%). Interestingly, body weights and lean body mass were lower in mARKO vs. control mice (–8%). The weight of the highly androgen-sensitive musculus levator ani was significantly reduced (–46%), whereas the weights of other peripheral skeletal muscles were not or only slightly reduced. mARKO mice had lower intra-abdominal fat but did not demonstrate a cortical or trabecular bone phenotype, indicating that selective ablation of the AR in myocytes affected male body composition but not skeletal homeostasis. Furthermore, muscle contractile performance in mARKO mice did not differ from their controls. Myocyte-specific AR ablation resulted in a conversion of fast toward slow fibers, without affecting muscle strength or fatigue. Similar results were obtained in ubiquitous AR deletion, showing lower body weight, whereas some but not all muscle weights were reduced. The percent slow fibers was increased, but no changes in muscle strength or fatigue could be detected. Together, our findings show that myocyte AR signaling contributes to the maintenance of muscle mass and fiber type regulation but not to muscle strength or fatigue. The levator ani weight remains the most sensitive and specific marker of AR-mediated anabolic action on muscle.

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