Estradiol modulates the expression pattern of myosin heavy chain subtypes via an ERα-mediated pathway in muscle-derived tissues and satellite cells

Background: Muscle-derived satellite cells (MDSCs) express MHC molecules intimately related to muscle function, which is supposed to be affected by local estrogen (E ₂ ) levels. However, cellular targets and molecular mechanisms involved are poorly understood. Methods: Genioglossus (GG) muscle tissues and MDSCs were derived from SHAM, ovariectomized or ovariectomized and 17 β-estradiol injected rats (n=10 / group). ERα, ERβ, MHC expression and underlying regulatory mechanisms were investigated by RT-PCR, western blot and immunohistochemistry, inter alia upon selective antagonist exposure and Si-RNA transfection. MDSC viability and cell cycle were examined by MTT and flow cytometry. Results: E ₂ upregulated MHC-I and downregulated MHC-IIb expression in MDSCs. E ₂ mediated effects on these molecules were inhibited by ERα-selective antagonist MPP and si-ERα, whereas they persisted upon exposure to ERβ-selective antagonist PHTPP. ERα was significantly higher expressed in muscle tissues compared to ERβ. ER positive stainings were fewer in the ovariectomized than in the SHAM group. Injection of E ₂ only increased the positive staining of ERα, but not of ERβ. Conclusion: Results suggest that E ₂ regulates MHC expression mainly through an ERα-mediated pathway with opposing effects on MHC-I and MHC-IIb. Thus, different hormonal processes that impact muscular pathophysiology presumably govern the functional properties of these molecules.