title: Extracellular signal-regulated kinase-mammalian target of rapamycin signaling and forkhead-box transcription factor 3a phosphorylation are involved in testosterone's effect on severe burn injury in a rat model.
abstract: BACKGROUND
  Testosterone and androgen receptor agonists have been known for a long time to prevent or reverse muscle wasting in burn injury patients, but the exact molecular mechanisms are not clear.
  
  
  OBJECTIVE
  To investigate the underlying molecular mechanisms of testosterone in severely burned rats.
  
  
  METHODS
  Severe burn injuries were induced by immersing the back of the rat in 100 °C water for 12 s. Rats were treated for 14 days with vehicle (burn group) or a physiological replacement dose of testosterone (B + T group) immediately after injury. Gene and protein expressions were assessed by real-time polymerase chain reaction and Western blot.
  
  
  RESULTS
  Testosterone improved glucose metabolism, reduced body weight loss, and attenuated tibialis anterior muscle mass loss and muscle protein breakdown. In rat tibialis anterior muscle, testosterone positively regulated the insulin-sensitive glucose transporters Glut3 and Glut4 genes and glycogen synthase 1 protein. These changes would be expected to improve glucose metabolism and nutrient availability in skeletal muscle. Administration of testosterone negatively regulated atrogin 1 (Fbxo32) by increasing total and phosphorylated Foxo3a (forkhead-box transcription factor 3a) levels and positively regulated the expression of the mammalian target of rapamycin (mTOR) and its downstream proteins p70S6 and S6 through mTOR-extracellular signal-regulated kinase phosphorylation.
  
  
  CONCLUSIONS
  RESULTS suggested that testosterone might regulate skeletal muscle glucose and protein metabolism following burn injury in part by affecting extracellular signal-regulated kinase-mTOR signaling and Foxo3a levels.
authors: Department of Burns and Plastic Surgery, Burns Institute, First Hospital Affiliated to General Hospital of PLA, Beijing, China.
authors: Li
authors: L
authors: Ma
authors: Chuanan
authors: C
authors: Shen
authors: Jiake
authors: J
authors: Chai
authors: Huinan
authors: H
authors: Yin
authors: Huping
authors: H
authors: Deng
authors: Rui
authors: R
authors: Feng
mesh_terms: D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D002056:Burns / Q000378:metabolism* / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D051274:Glucose Transporter Type 3 / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D013739:Testosterone / Q000494:pharmacology*
chemical_list: D000728:Androgens; C499515:FOXO3 protein, rat; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D051274:Glucose Transporter Type 3; D051275:Glucose Transporter Type 4; C495690:Slc2a3 protein, rat; C495694:Slc2a4 protein, rat; D013739:Testosterone; C546845:mTOR protein, rat; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D005947:Glucose