Non-Genomic Effects of Trenbolone Acetate on Bovine Satellite Cell Proliferation

Abstract Text:

Androgen treatment improves skeletal muscle growth in a number of species; however the mechanism responsible for this improved muscle growth has not been fully elucidated. Trenbolone acetate (TBA), a testosterone analog that does not undergo aromatization to estradiol, has been shown to increase proliferation and protein synthesis rates and decrease protein degradation rate in bovine satellite cell (BSC) cultures. This is particularly significant because satellite cells are the source of nuclei needed to support postnatal muscle fiber hypertrophy and are thus crucial in determining the rate and extent of muscle growth although, the mechanism responsible for these effects of TBA on BSC has not been fully determined.  The classical genomic actions of testosterone in which the androgen receptor acts as a ligand inducible transcription factor modulating target gene transcription has been well characterized. However, our recent studies have indicated that TBA may also initiate a quicker, non-genomic, response that involves release of membrane bound heparin binding epidermal growth factor-like growth factor (hbEGF) which then binds to and activates the epidermal growth factor receptor (EGFR). To determine whether this non-genomic pathway is involved in TBA-stimulated BSC proliferation we analyzed the effects of treating BSC with AG1478, a specific EGFR tyrosine kinase inhibitor, and CRM197, a specific inhibitor of hbEGF, on TBA-stimulated proliferation rate (³H-Thymidine incorporation). As expected, BSC cultures treated with 10nm TBA showed significantly (P < 0.05) increased proliferation rate when compared to control cultures. Additionally, treatment with 5 ng hbEGF/ml stimulated proliferation in BSC cultures (P < 0.05). Treatment with AG1478 significantly (P < 0.05) suppressed TBA-induced increases in proliferation. Additionally, in the presence of CRM197, TBA induced increases in proliferation were significantly (P < 0.05) decreased. These data indicate that hbEGF and the EGFR may play a role in TBA-mediated increases in BSC proliferation. Further, these findings demonstrate that testosterone/TBA may stimulate increases in skeletal muscle growth utilizing a non-genomic mechanism.

Keywords: Epidermal Growth Factor Receptor, Satellite Cells, Trenbolone Acetate