| dc.description.abstract | It is well known that androgen supplementation can increase muscle strength. Some athletes take large amounts of androgen to increase muscle mass and strength. It is well-documented that testosterone, a natural circulatory androgen, administration to young, hypogonadal men and older men with lower testosterone levels stimulates muscle protein synthesis. The physiological effects of androgen administration to muscle are obvious. However, the underlying molecular mechanisms are still unknown. The myogenic regulatory factors (MRFs), including MyoD, Myf-5, myogenin, and MRF4, form a family of muscle-specific transcription factors that control skeletal muscle lineage specification and terminal differentiation. It has been reported recently that Wnt3a functions via β-catenin to induce the expression of Mox1, Pax3 and Gli2, which then activate the expression of MRFs. We hypothesized that androgen receptor (AR) may work somewhere along this pathway to regulate MRF expression and get involved in the myogenic commitment. In order to enhance the effects of AR on myogenic commitment, AR was over-expressed in cells by adenovirus and retrovirus mediated over-expression systems. C3H 10T1/2 cells was infected with adenovirus and retrovirus carrying AR cDNA, so that AR was over-expressed either transiently or permanently in cells respectively. 5-azacytidine treated C3H 10T1/2 cells have been proven to be able to switch to myoblast. Therefore, we treated the S-AR 10T1/2 cells with 5-azacytidine in the presence and absence of androgen to dissect the AR-mediated myogenesis pathway. Interestingly, 5-azacytidine treated S-AR 10T1/2 cells were able to commit to myogenic lineage in the absence of androgen with higher percentage as compared to that in the presence of androgen. In addition, flutamide, one type of anti-androgen, was unable to block the myogenic commitment in S-AR 10T1/2 cells. Hence, we suggest that AR may function in the cytoplasm to enhance myogenic commitment through either, Wnt3a-β-catenin mediated pathway or signaling pathways, or both of them. | en_US |