title: Glucocorticoids retard skeletal muscle development and myoblast protein synthesis through a mechanistic target of rapamycin (mTOR)-signaling pathway in broilers (Gallus gallus domesticus).
abstract: Glucocorticoids exert a well-known catabolic protein action on skeletal muscle. The mechanistic target of rapamycin (mTOR) signaling pathway acts as a central regulator of protein metabolism. Whether glucocorticoids regulate protein synthesis through the mTOR pathway in skeletal muscle of chickens remains unknown. This study was performed to characterize the effect of glucocorticoids on the mTOR pathway in skeletal muscle development in chickens, and on protein synthesis in cultured embryonic myoblasts. Male 29-d-old chickens were given a dexamethasone injection (2 mg/kg) twice per day for 4 d (n = 16). Chicken embryonic myoblasts were exposed to dexamethasone for 24 h (100 µmol/L, n = 4 cultures). The interaction between dexamethasone and leucine was also investigated. ANOVA and Duncan's multiple test were used to analyze the effects of the dexamethasone and leucine treatments. The results showed that dexamethasone decreased body weight gain, body weight, and feed efficiency. Protein synthesis was inhibited by in vitro dexamethasone exposure. Phosphorylation of mTOR and ribosomal protein S6 protein kinase (p70S6K) were inhibited by dexamethasone, suggesting the mTOR pathway may be involved in dexamethasone-regulated muscle protein synthesis. Phosphorylation of AMP-activated protein kinase (AMPK) was not altered in vitro but was reduced in vivo by dexamethasone. These results imply that the mTOR and AMPK pathways are both involved in retarding muscle development and protein synthesis by glucocorticoids, but the mTOR pathway is a critical point linking glucocorticoid and protein synthesis. Leucine, at least partially, inhibited the effects of dexamethasone on protein synthesis via the mTOR pathway.
authors.affiliation: a Department of Animal Science , Shandong Agricultural University , Taian , Shandong , PR China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Wang
authors.affiliation: a Department of Animal Science , Shandong Agricultural University , Taian , Shandong , PR China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Jia
authors.affiliation: a Department of Animal Science , Shandong Agricultural University , Taian , Shandong , PR China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Xiao
authors.affiliation: a Department of Animal Science , Shandong Agricultural University , Taian , Shandong , PR China.
authors.forename: Hongchao
authors.initials: H
authors.lastname: Jiao
authors.affiliation: a Department of Animal Science , Shandong Agricultural University , Taian , Shandong , PR China.
authors.forename: Hai
authors.initials: H
authors.lastname: Lin
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D002645:Chickens; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D008297:Male; D024510:Muscle Development / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D032446:Myoblasts / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D005938:Glucocorticoids; D003907:Dexamethasone; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D020123:Sirolimus
keywords: Chickens; dexamethasone; leucine; muscle development; protein metabolism; signal pathway