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. Issue 1 (January 2015)

• Record Type: Journal Article
• Authors: Ma, Li; Shen, Chuanan; Chai, Jiake; Yin, Huinan; Deng, Huping; Feng, Rui
• Is Part Of: Shock. Volume 43:Issue 1(2015:Jan.)
• Publication Date: 2015-01
• Subjects: Shock -- Periodicals; Shock -- Periodicals; Choc (Pathologie) -- Périodiques; Shock; Periodicals; 616.0475
• DOI: 10.1097/SHK.0000000000000244
• Languages: English
• ISSNs: 1073-2322

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>ABSTRACT</title> <p> <bold>Background:</bold> 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. <bold>Objective:</bold> To investigate the underlying molecular mechanisms of testosterone in severely burned rats. <bold>Methods:</bold> 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. <bold>Results:</bold> 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. <bold>Conclusions:</bold> 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.</p> </sec> </abstract>