title: Role of glucocorticoids in the molecular regulation of muscle wasting.
abstract: 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.
authors: Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors: Michael
authors: M
authors: Menconi
authors: Moin
authors: M
authors: Fareed
authors: Patrick
authors: P
authors: O'Neal
authors: Vitaliy
authors: V
authors: Poylin
authors: Wei
authors: W
authors: Wei
authors: Per-Olof
authors: PO
authors: Hasselgren
mesh_terms: 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*
chemical_list: 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