Transcriptional regulation of myotrophic actions by testosterone and trenbolone on androgen-responsive muscle

abstract Androgens regulate body composition and skeletal muscle mass in males, but the molecular mechanismsare not fully understood. Recently, we demonstrated that trenbolone (a potent synthetic testosteroneanalogue that is not a substrate for 5-alpha reductase or for aromatase) induces myotrophic effects inskeletal muscle without causing prostate enlargement, which is in contrast to the known prostate enlarg-ing effects of testosterone. These previous results suggest that the 5 a -reduction of testosterone is notrequired for myotrophic action. We now report differential gene expression in response to testosteroneversus trenbolone in the highly androgen-sensitive levator ani/bulbocavernosus (LABC) muscle complexof the adult rat after 6 weeks of orchiectomy (ORX), using real time PCR. The ORX-induced expression ofatrogenes (Muscle RING-finger protein-1 [MuRF1] and atrogin-1) was suppressed by both androgens,with trenbolone producing a greater suppression of atrogin-1 mRNA compared to testosterone. Bothandrogens elevated expression of anabolic genes (insulin-like growth factor-1 and mechano-growthfactor) after ORX. ORX-induced increases in expression of glucocorticoid receptor (GR) mRNA were sup-pressed by trenbolone treatment, but not testosterone. In ORX animals, testosterone promoted WNT1-inducible-signaling pathway protein 2 (WISP-2) gene expression while trenbolone did not. Testosteroneand trenbolone equally enhanced muscle regeneration as shown by increases in LABC mass and in proteinexpression of embryonic myosin by western blotting. In addition, testosterone increased WISP-2 proteinlevels. Together, these findings identify specific mechanisms by which testosterone and trenbolone mayregulate skeletal muscle maintenance and growth. 2014 Elsevier Inc. All rights reserved.