Muscle-specific androgen receptor deletion shows limited actions in myoblasts but not in myofibers in different muscles in vivo

作者：Rana Kesha^*; Chiu Maria W S; Russell Patricia K; Skinner Jarrod P; Lee Nicole K L; Fam Barbara C; Zajac Jeffrey D; MacLean Helen E

来源：Journal of Molecular Endocrinology, 2016, 57(2): 125-138.

DOI：10.1530/JME-15-0320

• androgen receptor
• muscle
• myoblasts
• myofibers

The aim of this study was to investigate the direct muscle cell-mediated actions of androgens by comparing two different mouse lines. The cre-loxP system was used to delete the DNA-binding activity of the androgen receptor (AR) in mature myofibers (MCK mAR(Delta ZF2)) in one model and the DNA-binding activity of the AR in both proliferating myoblasts and myofibers (alpha-actin mAR(Delta ZF2)) in another model. We found that hind-limb muscle mass was normal in MCK mAR(Delta ZF2) mice and that relative mass of only some hind-limb muscles was reduced in alpha-actin mAR(Delta ZF2) mice. This suggests that myoblasts and myofibers are not the major cellular targets mediating the anabolic actions of androgens on male muscle during growth and development. Levator ani muscle mass was decreased in both mouse lines, demonstrating that there is a myofiber-specific effect in this unique androgen-dependent muscle. We found that the pattern of expression of genes including c-myc, Fzd4 and Igf2 is associated with androgen-dependent changes in muscle mass; therefore, these genes are likely to be mediators of anabolic actions of androgens. Further research is required to identify the major targets of androgen actions in muscle, which are likely to include indirect actions via other tissues.

• 出版日期2016-8