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1 Copenhagen Muscle Research Centre, Copenhagen , Denmark
2 Copenhagen Muscle Research Centre, August Krogh Institute/Institute for Exercise + Sport Science, Copenhagen N., Denmark
3 Department of Molecular Biology, University of Copenhagen, Copenhagen, Denmark
* To whom correspondence should be addressed. E-mail: lundby{at}idraet.au.dk.
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 weeks) 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, increased transferrin receptor and MRF-4 mRNA content within 10 hours after injection. Plasma hormones remained unaltered. With Capillarisation 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 fibre area (0.84 ± 0.2 vs 0.72 ± 0.3 mm2), capillaries per fibre (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.
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