Muscle Cellular and Molecular Physiology Research Group, Institute for Sport and Physical Activity Research, University of Bedfordshire, Bedford, United Kingdom.
Med Sci Sports Exerc. 2012 Apr;44(4):610-5. doi: 10.1249/MSS.0b013e318237c5c0.
The mechanism whereby anabolic androgens are associated with hypertrophy of skeletal muscle is incompletely understood but may involve an interaction with locally generated insulin-like growth factor (IGF) 1. The present investigation utilized a cell culture model of human skeletal muscle-derived cell maturation to test the hypothesis that androgens increase differentiation of human muscle precursor cells in vitro and to assess effects of androgen with or without IGF-1 on IGF-1 messenger RNA (mRNA) expression in human muscle precursor cells.
Differentiation of muscle-derived cells was induced under standard low-serum conditions. Cultures were then exposed to androgen (testosterone (T)) at 50, 100, and 500 nM or IGF-1 (10-50 ng·mL⁻¹). Immunocytochemistry and real-time polymerase chain reaction (RT-PCR) were used to assess effects of androgens and IGF-1 after 3- (early) or 7-d (late) muscle differentiation, respectively; RT-PCR was used to quantify the effects on androgen receptor expression.
Under low-serum conditions, 3-d exposure to androgens or IGF-1 or both resulted in no significant increase in cellular myogenic commitment. After 7-d exposure, however, T and IGF-1 were both found to increase fusion index with no observable synergistic effect. T also increased IGF-1 mRNA generation (P < 0.0001), whereas exogenous IGF-1 (P < 0.001) reduced IGF-1 mRNA transcription relative to control. The T effect was reversible after treatment with flutamide, an androgen receptor antagonist.
Both T and IGF-1 increase myogenic commitment after 7-d exposure to a differentiation medium. With T causing a concomitant increase in IGF-1 mRNA underpinning IGF-1 as a central mediator in the cellular pathways associated with muscle hypertrophy, including those affected by androgens. The novel system described has the potential for elucidating the pattern of growth factor effects associated with androgens in skeletal muscle.
合成代谢雄激素与骨骼肌肥大相关的机制尚不完全清楚，但可能涉及与局部产生的胰岛素样生长因子 (IGF) 1 的相互作用。本研究利用人骨骼肌源性细胞成熟的细胞培养模型，检验雄激素在体外增加人肌肉前体细胞分化的假说，并评估雄激素与 IGF-1 联合或不联合对人肌肉前体细胞 IGF-1 信使 RNA (mRNA) 表达的影响。
在标准低血清条件下诱导肌肉源性细胞分化。然后，将培养物暴露于雄激素（睾丸酮（T））50、100 和 500 nM 或 IGF-1（10-50 ng·mL⁻¹）。免疫细胞化学和实时聚合酶链反应（RT-PCR）分别用于评估 3 天（早期）或 7 天（晚期）肌肉分化后雄激素和 IGF-1 的作用；RT-PCR 用于量化对雄激素受体表达的影响。
在低血清条件下，3 天暴露于雄激素或 IGF-1 或两者均未导致细胞肌生成承诺显著增加。然而，在 7 天暴露后，T 和 IGF-1 均被发现增加融合指数，没有观察到协同作用。T 还增加了 IGF-1 mRNA 的产生（P < 0.0001），而外源性 IGF-1（P < 0.001）相对于对照降低了 IGF-1 mRNA 转录。用雄激素受体拮抗剂氟他胺处理后，T 的作用是可逆的。
T 和 IGF-1 在分化培养基中暴露 7 天后均增加肌生成承诺。T 导致 IGF-1 mRNA 同时增加，IGF-1 作为与肌肉肥大相关的细胞途径中的中枢介质，包括受雄激素影响的途径。所描述的新系统具有阐明与雄激素相关的生长因子在骨骼肌中作用模式的潜力。
