Estrogen receptor beta is involved in skeletal muscle hypertrophy induced by the phytoecdysteroid ecdysterone

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  • Maria Kristina Parr
    Center for Preventive Doping Research German Sport University Cologne Germany
  • Piwen Zhao
    School of Preclinical Medicine Beijing University of Chinese Medicine Bejing P. R. China
  • Oliver Haupt
    Center for Preventive Doping Research German Sport University Cologne Germany
  • Sandrine Tchoukouegno Ngueu
    Center for Preventive Doping Research German Sport University Cologne Germany
  • Jonas Hengevoss
    Center for Preventive Doping Research German Sport University Cologne Germany
  • Karl Heinrich Fritzemeier
    Bayer Pharma AG Berlin Germany
  • Marion Piechotta
    Clinic for Cattle, Endocrinology Laboratory University of Veterinary Medicine Hannover Hannover Germany
  • Nils Schlörer
    Institute of Organic Chemistry University of Cologne Germany
  • Peter Muhn
    Bayer Pharma AG Berlin Germany
  • Wen‐Ya Zheng
    Center for Preventive Doping Research German Sport University Cologne Germany
  • Ming‐Yong Xie
    State Key Laboratory of Food Science and Technology Nanchang University Nanchang P. R. China
  • Patrick Diel
    Center for Preventive Doping Research German Sport University Cologne Germany

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<jats:sec><jats:title>Scope</jats:title><jats:p>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).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>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.</jats:p></jats:sec>

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