Role of glucocorticoids in the molecular regulation of muscle wasting.
OBJECTIVE
To review glucocorticoid-regulated molecular mechanisms of muscle wasting.


METHODS
Review of recent literature describing the role of glucocorticoids in the regulation of proteolytic mechanisms, transcription factors, and nuclear cofactors in skeletal muscle during various catabolic conditions.


RESULTS
Catabolic doses of glucocorticoids induce muscle atrophy both in vivo and in vitro by stimulating protein breakdown and inhibiting protein synthesis. Signaling pathways that regulate muscle protein synthesis at the translational level are inhibited by glucocorticoids. Glucocorticoids increase the expression and activity of the ubiquitin-proteasome pathway, a major proteolytic mechanism of muscle atrophy. The expression and activity of muscle wasting-related transcription factors, including C/EBPbeta and delta and Forkhead box O 1, 3, and 4, as well as the nuclear cofactor p300, are up-regulated by glucocorticoid excess.


CONCLUSIONS
Muscle wasting in various catabolic conditions is, at least in part, regulated by glucocorticoids. The role of glucocorticoids in muscle wasting is complex and reflects regulation at the molecular level of multiple mechanisms influencing both synthesis and degradation of muscle proteins.
Menconi
Michael
M
Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Fareed
Moin
M
O'Neal
Patrick
P
Poylin
Vitaliy
V
Wei
Wei
W
Hasselgren
Per-Olof
PO
D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005938:Glucocorticoids / Q000097:blood / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007930:Leucine / Q000378:metabolism; D009124:Muscle Proteins / Q000096:biosynthesis; D018482:Muscle, Skeletal / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000502:physiology; D014452:Ubiquitins / Q000502:physiology; D019282:Wasting Syndrome / Q000378:metabolism*
C083058:C-EPB transcription factor; D022762:CCAAT-Enhancer-Binding Proteins; D051858:Forkhead Transcription Factors; D005938:Glucocorticoids; D007328:Insulin; D009124:Muscle Proteins; D009687:Nuclear Proteins; D014452:Ubiquitins; D007334:Insulin-Like Growth Factor I; D046988:Proteasome Endopeptidase Complex; D007930:Leucine