Casted-immobilization downregulates glucocorticoid receptor expression in rat slow-twitch soleus muscle.
OBJECTIVE
Glucocorticoids bind to the glucocorticoid receptor (GR) and increase catabolism of muscle proteins via the ubiquitin-proteasome pathway. Activation of β(2)-adrenergic receptor (β(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 β(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 β(2)-AR was analyzed by real-time RT-PCR and western blotting. In addition, we analyzed plasma catecholamine and corticosterone concentrations by ELISA.


RESULTS
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 β(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 β(2)-AR mRNA in the SOL muscle. Plasma catecholamine and corticosterone concentrations, however, were largely unaffected by casted-immobilization during the experimental period.


CONCLUSIONS
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 β(2)-AR gene, via downregulation of GR expression in slow-twitch muscle.
Laboratory of Physiological Sciences, Faculty of Human Sciences, Waseda University, 2-579-15 Mikajima, Tokorozawa, Saitama 359-1192, Japan.
Shogo
S
Sato
Hideki
H
Suzuki
Hisaya
H
Tsujimoto
Ken
K
Shirato
Kaoru
K
Tachiyashiki
Kazuhiko
K
Imaizumi
D000818:Animals; D015153:Blotting, Western; D015536:Down-Regulation; D007103:Immobilization; D008297:Male; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D009133:Muscular Atrophy / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014158:Transcription, Genetic
D012333:RNA, Messenger; D018343:Receptors, Adrenergic, beta-2; D011965:Receptors, Glucocorticoid