UNASSIGNED: We have previously highlighted the ability of @entity251 (T) to improve differentiation and @entity1184 in fusion impaired myoblasts that display reduced @entity1184 via multiple @entity14485 ( @entity14485 ) versus their parental controls (CON); an observation which is abrogated via @entity3115 / @entity1994 inhibition (Deane et al. 2013). However, whether the most predominant molecular mechanism responsible for T induced @entity1184 occurs directly via @entity342 receptor or indirectly via IGF-IR/ @entity3115 / @entity1994 pathway is currently debated. @entity14485 and CON C2C12 muscle cells were exposed to low serum conditions in the presence or absence of T (100  nM)      inhibitors of @entity1984 ( @entity12194 /F, 40   m) and IGF-IR ( @entity69938 /PPP, 150  nM) for 72  h and 7  days (early/late muscle differentiation respectively). T increased @entity1984 and @entity1994 abundance, @entity20476 gene expression, and @entity1184 , but not @entity8837 activity in both CON and @entity14485 cell types. @entity1994 activity was not increased significantly in either cell type with T. @entity251 was  also unable to promote early differentiation in the presence of IGF-IR inhibitor (PPP) yet still able to promote appropriate later @entity1184 and @entity1984 abundance despite IGF-IR inhibition. The addition of the @entity1984 inhibitor powerfully attenuated all T induced increases in differentiation and @entity1184 with corresponding reductions in @entity1984 abundance, phosphorylated @entity1994 , @entity8837 and gene expression of IGF-IR, @entity14814 and @entity20476 with increases in myostatin mRNA  in both cell types. Interestingly, despite basally reduced differentiation and @entity1184 , @entity14485 cells showed larger T induced increases in @entity1984 abundance vs. CON cells, a response abrogated in the presence of @entity1984 but not IGF-IR inhibitors. Furthermore, T induced increases in @entity1994 abundance were sustained despite the presence of IGF-IR inhibition in @entity14485 cells only. Importantly, @entity12194 alone reduced IGF-IR mRNA in both cell types across time points, with an observed reduction in activity of @entity13436 and @entity1994 , suggesting that IGF-IR was transcriptionally regulated by @entity1984 . However, where @entity251 increased @entity1984 protein content there was no increases observed in IGF-IR gene expression. This suggested that sufficient @entity1984 was important to enable normal IGF-IR expression and downstream signalling, yet elevated levels of @entity1984 due to @entity251 had no further effect on IGF-IR  mRNA, despite @entity251 increasing @entity1994 abundance in the presence of IGF-IR inhibitor. In conclusion, testosterones ability to improve differentiation and @entity1184 occurred predominately via increases in @entity1984 and @entity1994 abundance in both CON and @entity14485 cells, with fusion impaired cells ( @entity14485 ) showing an increased responsiveness to T induced @entity1984 levels. Finally, T induced @entity1184 (but not early differentiation) occurred independently of upstream IGF-IR input, however it was apparent   that normal @entity1984 function in basal conditions was required for adequate IGF-IR gene expression and downstream @entity13436 / @entity1994 activity.

XXXX enables growth and @entity1184 in fusion impaired myoblasts that display myotube atrophy: deciphering the role of @entity342 and IGF-I receptors.

@entity1984 :: ('MESH:D013734', 'Disease') :: ['AR'] @entity20476 :: ('17928(Tax:10090)', 'Gene') :: ['myogenin'] @entity251 :: ('MESH:D013739', 'Chemical') :: ['testosterone', 'Testosterone'] @entity3115 :: ('18708(Tax:10090)', 'Gene') :: ['PI3K'] @entity69938 :: ('MESH:C415032', 'Chemical') :: ['picropodophyllin'] @entity14814 :: ('17927(Tax:10090)', 'Gene') :: ['myoD'] @entity1184 :: ('MESH:D006984', 'Disease') :: ['myotube hypertrophy', 'hypertrophy', 'increases in myotube hypertrophy'] @entity12194 :: ('MESH:D005485', 'Chemical') :: ['flutamide'] @entity14485 :: ('MESH:D005671', 'Disease') :: ['population doublings', 'PD'] @entity13436 :: ('26413(Tax:10090)', 'Gene') :: ['ERK'] @entity1994 :: ('11651(Tax:10090)', 'Gene') :: ['Akt'] @entity342 :: ('CHEBI:50113', 'Chemical') :: ['androgen'] @entity8837 :: ('26417;26413', 'Gene') :: ['ERK1/2']
@entity251 :: (MESH:D013739,Chemical) :: ['Testosterone']
