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 (GRα and GRβ) in humans. While the role of GRα is well characterized, GRβ remains an elusive player in GC signalling. To elucidate basic characteristics of GC signalling in the regenerating human skeletal muscle we assessed GRα and GRβ expression pattern in cultured human myoblasts and myotubes and their response to 24-hour dexamethasone (DEX) treatment. There was no difference in GRα mRNA and protein expression or DEX-mediated GRα down-regulation in myoblasts and myotubes. GRβ mRNA level was very low in myoblasts and remained unaffected by differentiation and/or DEX. GRβ 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 GRβ mRNA expression and inability to detect GRβ protein suggests that GRβ is not a major player in the early stages of human skeletal muscle regeneration.