Estrogen receptor beta is involved in skeletal muscle hypertrophy induced by the phytoecdysteroid ecdysterone
Article first published online: 27 JUN 2014
© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 58, Issue 9, pages 1861–1872, September 2014
How to Cite
Parr, M. K., Zhao, P., Haupt, O., Ngueu, S. T., Hengevoss, J., Fritzemeier, K. H., Piechotta, M., Schlörer, N., Muhn, P., Zheng, W.-Y., Xie, M.-Y. and Diel, P. (2014), Estrogen receptor beta is involved in skeletal muscle hypertrophy induced by the phytoecdysteroid ecdysterone. Mol. Nutr. Food Res., 58: 1861–1872. doi: 10.1002/mnfr.201300806
- Issue published online: 8 SEP 2014
- Article first published online: 27 JUN 2014
- Manuscript Accepted: 30 APR 2014
- Manuscript Revised: 28 APR 2014
- Manuscript Received: 4 NOV 2013
- China Scholarship Council
- Sino-German Center. Grant Number: GZ731
- International Science and Technology Cooperation Projects. Grant Number: 2010DFA31780
- Dietary supplement;
- Estrogen receptor beta;
- Skeletal muscle;
- Traditional Chinese medicine
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.