Center for Preventive Doping Research, German Sport University, Cologne, Germany; Institute of Pharmacy, Freie Universität Berlin, Germany.
Mol Nutr Food Res. 2014 Sep;58(9):1861-72. doi: 10.1002/mnfr.201300806. Epub 2014 Jun 27.
The phytoectysteroid ecdysterone (Ecdy) was reported to stimulate protein synthesis and enhance physical performance. The aim of this study was to investigate underlying molecular mechanisms particularly the role of ER beta (ERβ).
In male rats, Ecdy treatment increased muscle fiber size, serum IGF-1 increased, and corticosteron and 17β-estradiol (E2) decreased. In differentiated C2C12 myoblastoma cells, treatment with Ecdy, dihydrotestosterone, IGF-1 but also E2 results in hypertrophy. Hypertrophy induced by E2 and Ecdy could be antagonized with an antiestrogen but not by an antiandrogen. In HEK293 cells transfected with ER alpha (ERα) or ERβ, Ecdy treatment transactivated a reporter gene. To elucidate the role of ERβ in Ecdy-mediated muscle hypertrophy, C2C12 myotubes were treated with ERα (ALPHA) and ERβ (BETA) selective ligands. Ecdy and BETA treatment but not ALPHA induced hypertrophy. The effect of Ecdy, E2, and BETA could be antagonized by an ERβ-selective antagonist (ANTIBETA). In summary, our results indicate that ERβ is involved in the mediation of the anabolic activity of the Ecdy.
These findings provide new therapeutic perspectives for the treatment of muscle injuries, sarcopenia, and cachectic disease, but also imply that such a substance could be abused for doping purposes.
植物甾体蜕皮激素蜕皮甾酮（Ecdy）被报道能刺激蛋白质合成和增强身体表现。本研究旨在探究其潜在的分子机制，特别是 ERβ（雌激素受体β）的作用。
在雄性大鼠中，Ecdy 处理增加了肌肉纤维的大小，血清 IGF-1 增加，而皮质酮和 17β-雌二醇（E2）减少。在分化的 C2C12 成肌细胞瘤细胞中，Ecdy、二氢睾酮、IGF-1 以及 E2 的处理导致细胞肥大。E2 和 Ecdy 诱导的肥大可以被抗雌激素拮抗，但不能被抗雄激素拮抗。在转染了 ERα（ERα）或 ERβ 的 HEK293 细胞中，Ecdy 处理可使报告基因反式激活。为了阐明 ERβ 在 Ecdy 介导的肌肉肥大中的作用，用 ERα（ALPHA）和 ERβ（BETA）选择性配体处理 C2C12 肌管。Ecdy 和 BETA 处理而非 ALPHA 诱导了肥大。Ecdy、E2 和 BETA 的作用可被 ERβ 选择性拮抗剂（ANTIBETA）拮抗。总之，我们的结果表明 ERβ 参与了 Ecdy 的合成代谢活性的介导。
这些发现为治疗肌肉损伤、肌肉减少症和恶病质疾病提供了新的治疗前景，但也暗示这种物质可能被滥用于兴奋剂目的。
