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Erythropoietin receptor in human skeletal muscle and the effects of acute and long-term injections with recombinant human erythropoietin on the skeletal muscle

¹Copenhagen Muscle Research Centre, ²Rigshospitalet section 7652, Copenhagen, ³Department of Sport Science, Århus, Denmark, ⁴Department for Exercise and Sport Science, University of Copenhagen; and ⁵Centre of Inflammation and Metabolism, Department of Molecular Biology, University of Copenhagen, Denmark

Submitted 13 November 2007 ; accepted in final form 23 January 2008

The presence and potential physiological role of the erythropoietin receptor (Epo-R) were examined in human skeletal muscle. In this study we demonstrate that Epo-R is present in the endothelium, smooth muscle cells, and in fractions of the sarcolemma of skeletal muscle fibers. To study the potential effects of Epo in human skeletal muscle, two separate studies were conducted: one to study the acute effects of a single Epo injection on skeletal muscle gene expression and plasma hormones and another to study the effects of long-term (14 wk) Epo treatment on skeletal muscle structure. Subjects (n = 11) received a single Epo injection of 15,000 IU (double blinded, cross over, placebo). A single Epo injection reduced myoglobin and increased transferrin receptor and MRF-4 mRNA content within 10 h after injection. Plasma hormones remained unaltered. Capillarization and fiber hypertrophy was studied in subjects (n = 8) who received long-term Epo administration, and muscle biopsies were obtained before and after. Epo treatment did not alter mean fiber area (0.84 ± 0.2 vs. 0.72 ± 0.3 mm²), capillaries per fiber (4.3 ± 0.5 vs. 4.4 ± 1.3), or number of proliferating endothelial cells. In conclusion, the Epo-R is present in the vasculature and myocytes in human skeletal muscle, suggesting a role in both cell types. In accordance, a single injection of Epo regulates myoglobin, MRF-4, and transferrin receptor mRNA levels. However, in contrast to our hypothesis, prolonged Epo administration had no apparent effect on capillarization or muscle fiber hypertrophy.

angiogenesis; hypertrophy; vascular endothelial growth factor; rHuEpo; cancer; tumor

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