Casted-immobilization downregulates glucocorticoid receptor expression in rat slow-twitch soleus muscle.
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AIMS: Glucocorticoids bind to the glucocorticoid receptor (GR) and increase catabolism of muscle proteins via the ubiquitin-proteasome pathway. Activation of (2)-adrenergic receptor ((2)-AR) in skeletal muscle has been shown to induce muscle hypertrophy by promoting muscle protein synthesis and/or attenuating protein degradation. The aim of this study was to investigate the correlation between disuse-induced muscle atrophy, and expression of GR and (2)-AR. METHODS: Rats were subjected to casted-immobilization (knee and foot arthrodesis), a model for muscle disuse, for 10 days. Fast-twitch (extensor digitorum longus: EDL) and slow-twitch (soleus: SOL) muscles were isolated and subsequently used for analysis. The expression of GR and (2)-AR was analyzed by real-time RT-PCR and western blotting. In addition, we analyzed plasma catecholamine and corticosterone concentrations by ELISA. KEY FINDINGS: Casted-immobilization-induced muscle atrophy was much greater in the SOL muscle than in the EDL muscle. Casted-immobilization decreased the expression of GR mRNA and protein in the SOL muscle but not in the EDL muscle. Although the expression of (2)-AR protein in the cytosol and membrane-rich fractions was not changed by casted-immobilization in either muscle, casted-immobilization decreased the expression of (2)-AR mRNA in the SOL muscle. Plasma catecholamine and corticosterone concentrations, however, were largely unaffected by casted-immobilization during the experimental period. SIGNIFICANCE: This study provides evidence that casted-immobilization-induced muscle disuse downregulates GR expression in slow-twitch muscle. These results suggest that muscle disuse suppresses glucocorticoid signals, such as muscle protein breakdown and transcription of the (2)-AR gene, via downregulation of GR expression in slow-twitch muscle.
