Expression of Glucocorticoid Receptors in the Regenerating Human Skeletal Muscle

Many stress conditions are accompanied by skeletal muscle dysfunction and regeneration, which is essentially a recapitulation of the embryonic development. However, regeneration usually occurs under conditions of hypothalamus-pituitary-adrenal gland axis activation and therefore increased glucocorticoid (GC) levels. Glucocorticoid receptor (GR), the main determinant of cellular responsiveness to GCs, exists in two isoforms (GR alpha and GR beta) in humans. While the role of GRa is well characterized, GR beta remains an elusive player in GC signalling. To elucidate basic characteristics of GC signalling in the regenerating human skeletal muscle we assessed GRa and GR beta expression pattern in cultured human myoblasts and myotubes and their response to 24-hour dexamethasone (DEX) treatment. There was no difference in GRa mRNA and protein expression or DEX-mediated GRa down-regulation in myoblasts and myotubes. GR beta mRNA level was very low in myoblasts and remained unaffected by differentiation and/or DEX. GR beta protein could not be detected. These results indicate that response to GCs is established very early during human skeletal muscle regeneration and that it remains practically unchanged before innervation is established. Very low GR beta mRNA expression and inability to detect GR beta protein suggests that GR beta is not a major player in the early stages of human skeletal muscle regeneration.