Wannenes Francesca, Caprio Massimiliano, Gatta Lucia, Fabbri Andrea, Bonini Sergio, Moretti Costanzo
Department of Sciences of Human Movement and Sport, IUSM-University of Sport and Movement Sciences, Rome, Italy.
Mol Cell Endocrinol. 2008 Sep 24;292(1-2):11-9. doi: 10.1016/j.mce.2008.05.018. Epub 2008 Jun 7.
The Androgen Receptor (AR) pathway is involved in the development of skeletal muscle but the molecular basis of androgen-related myogenic enhancement is still unclear. We have investigated AR expression and localization during myoblasts-myotubes differentiation in skeletal muscle cell line C2C12. AR expression increases during proliferation and commitment phase and its levels remain elevated in myotubes. In proliferating and committed cells in the absence of testosterone, AR protein localizes in the nuclei whereas it is almost totally localized in the cytoplasm in myotubes. Low testosterone doses shift the receptor in the nuclei without increasing the amount of total protein. High doses of T induce a significant increase of AR expression during proliferation and differentiation. Little information is available on AR targets that drive the myogenic process. In our study, testosterone induces myogenin, myosin heavy chains (MyHC) and GRIP-1 expression, suggesting that AR and its coregulatory proteins are pivotal factors in skeletal muscle differentiation.
雄激素受体(AR)信号通路参与骨骼肌的发育,但雄激素相关的成肌增强作用的分子基础仍不清楚。我们研究了骨骼肌细胞系C2C12中肌成纤维细胞-肌管分化过程中AR的表达和定位。AR在增殖期和定向分化期表达增加,其水平在肌管中保持升高。在没有睾酮的增殖期和定向分化期细胞中,AR蛋白定位于细胞核,而在肌管中几乎完全定位于细胞质。低剂量睾酮使受体定位于细胞核,而不增加总蛋白量。高剂量睾酮在增殖期和分化期诱导AR表达显著增加。关于驱动成肌过程的AR靶点的信息很少。在我们的研究中,睾酮诱导生肌调节因子、肌球蛋白重链(MyHC)和GRIP-1的表达,表明AR及其共调节蛋白是骨骼肌分化的关键因素。