Mechanism of anabolic steroid stimulated bovine muscle growth: role of the epidermal growth factor receptor

Reiter, Brenda C.
2013-11

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Reiter_umn_0130M_14476.pdf (830.52 KB)

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http://hdl.handle.net/11299/162387
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Mechanism of anabolic steroid stimulated bovine muscle growth: role of the epidermal growth factor receptor

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2013-11

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Estradiol (E2) enhances muscle growth in a number of species; however, the mechanism by which E2 enhances muscle growth is not known. Treatment with 10 nM E2 stimulates proliferation and protein synthesis and inhibits protein degradation in cultured bovine satellite cells (BSC). 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; however the mechanism responsible for these E2 induced effects is not clear. Studies in other tissues have suggested that E2 may stimulate proliferation by activating the G protein-coupled estrogen receptor (GPER)-1 (formerly known as G protein-coupled receptor 30). Activation of GPER-1 results in activation of matrix metalloproteinases which release heparin-binding epidermal growth factor (hb-EGF) from the cell membrane and released hb-EGF interacts with the Epidermal Growth Factor Receptor (EGFR) resulting in increased proliferation. As an initial step in determining if this mechanism is involved in the effects of E2 on bovine satellite cell cultures, we have shown that silencing EGFR expression utilizing a specific EGFR siRNA suppresses the ability of E2 to stimulate proliferation in BSC cultures. Additionally, treatment of BSC cultures with a specific MMP 2/9 inhibitor suppresses E2 stimulated proliferation (p < 0.05). Finally, treatment of BSC cultures with G15 or G36 (specific GPER-1 antagonists) suppresses E2 stimulated proliferation (p < 0.05). These data strongly suggest that E2 stimulated transactivation of EGFR via GPER-1 is at least partially responsible for E2 induced increases in proliferation in BSC cultures.

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University of Minnesota M.S. thesis. November 2013. Major: Animal Sciences. Advisors: Dr. William Dayton and Dr. Michael White. 1 computer file (PDF); v, 62 pages.

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