Session: SAT 338-357-Steroid Hormone Actions
Poster Board SAT-340
The anabolic androgenic potency of ECDY was studied in vivo in comparison to testosterone propionate (TP). Male Wistar rats were treated for 21 days sc either with ECDY, TP or placebo. TP and ECDY increased the fiber size of soleus and gastrocnemius muscle. No androgenic activity (determined as increased weight of prostate or seminal vesicle) was observed on administration of ECDY. To further elucidate the molecular mechanisms cell culture experiments were conducted using the mouse skeletal muscle cell line C2C12. Differentiation of C2C12 cells towards myotubes was induced. Subsequently, myotubes were incubated with ECDY, dihydrotestosterone (DHT), IGF-1, dexamethasone (DEX) or 17β-estradiol (E2). Treatment with ECDY, DHT, IGF-1 but also E2 resulted in increased myotube diameters, demonstrating a hypertrophic effect, whereas treatment with DEX decreased myotube diameter. Co-treatment with the antiandrogen flutamide only antagonized the hypertrophic effect of DHT. In contrast, co-treatment with an antiestrogen (ZK) antagonized the effects of E2 and ECDY. IGF-1 activity could neither be antagonized by FLU or ZK.
To elucidate whether ER alpha or beta is involved in the anabolic activity of ECDY and E2, C2C12 cells were treated with ER alpha (ALPHA) and ER beta (BETA) selective ligands. In addition myotubes were co-treated with ECDY and an ER beta selective antagonist (ANTIBETA). E2 co-treated with ANTIBETA served as control. Incubation with BETA resulted in an anabolic effect which could be antagonized by ZK. Moreover the anabolic effect of E2 could be antagonized by ANTIBETA.
In summary, these observations indicate that on activation of ER beta a direct anabolic activity is induced in vitro and in vivo. Moreover, the anabolic activity of the phytoecdysteroid ecdysterone is most likely mediated via ER beta. These findings provide new therapeutic perspectives for the treatment of muscle injuries, sarcopenia and cachectic disease.
Nothing to Disclose: MKP, OH, ST, KHF, PM, PRD
*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm
See more of: Abstracts - Orals, Featured Poster Presentations, and Posters