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 (E2) 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: E2 upregulated MHC-I and downregulated MHC-IIb expression in MDSCs. E2 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 E2 only increased the positive staining of ERα, but not of ERβ. Conclusion: Results suggest that E2 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.