PMID- 22087027
OWN - NLM
STAT- MEDLINE
DCOM- 20120305
LR  - 20211203
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Linking)
VI  - 153
IP  - 1
DP  - 2012 Jan
TI  - The type 1 insulin-like growth factor receptor (IGF-IR) pathway is mandatory for 
      the follistatin-induced skeletal muscle hypertrophy.
PG  - 241-53
LID - 10.1210/en.2011-1687 [doi]
AB  - Myostatin inhibition by follistatin (FS) offers a new approach for muscle mass 
      enhancement. The aim of the present study was to characterize the mediators 
      responsible for the FS hypertrophic action on skeletal muscle in male mice. 
      Because IGF-I and IGF-II, two crucial skeletal muscle growth factors, are induced 
      by myostatin inhibition, we assessed their role in FS action. First, we tested 
      whether type 1 IGF receptor (IGF-IR) is required for FS-induced hypertrophy. By 
      using mice expressing a dominant-negative IGF-IR in skeletal muscle, we showed 
      that IGF-IR inhibition blunted by 63% fiber hypertrophy caused by FS. Second, we 
      showed that FS caused the same degree of fiber hypertrophy in wild-type and 
      IGF-II knockout mice. We then tested the role of the signaling molecules 
      stimulated by IGF-IR, in particular the Akt/mammalian target of rapamycin 
      (mTOR)/70-kDa ribosomal protein S6 kinase (S6K) pathway. We investigated whether 
      Akt phosphorylation is required for the FS action. By cotransfecting a 
      dominant-negative form of Akt together with FS, we showed that Akt inhibition 
      reduced by 65% fiber hypertrophy caused by FS. Second, we evaluated the role of 
      mTOR in FS action. Fiber hypertrophy induced by FS was reduced by 36% in 
      rapamycin-treated mice. Finally, because the activity of S6K is increased by FS, 
      we tested its role in FS action. FS caused the same degree of fiber hypertrophy 
      in wild-type and S6K1/2 knockout mice. In conclusion, the IGF-IR/Akt/mTOR pathway 
      plays a critical role in FS-induced muscle hypertrophy. In contrast, induction of 
      IGF-II expression and S6K activity by FS are not required for the hypertrophic 
      action of FS.
FAU - Kalista, S
AU  - Kalista S
AD  - Pole of Endocrinology, Diabetes, and Nutrition, Institut de Recherche 
      Experimentale et Clinique, Universite Catholique de Louvain, Avenue Hippocrate 55 
      bte B1.55.06, B-1200 Brussels, Belgium. stephanie.kalista@uclouvain.be
FAU - Schakman, O
AU  - Schakman O
FAU - Gilson, H
AU  - Gilson H
FAU - Lause, P
AU  - Lause P
FAU - Demeulder, B
AU  - Demeulder B
FAU - Bertrand, L
AU  - Bertrand L
FAU - Pende, M
AU  - Pende M
FAU - Thissen, J P
AU  - Thissen JP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111115
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (DNA Primers)
RN  - 0 (Follistatin)
RN  - 0 (IGF2 protein, mouse)
RN  - 0 (Recombinant Proteins)
RN  - 0 (follistatin, 288-amino acid isoform)
RN  - 67763-97-7 (Insulin-Like Growth Factor II)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - DNA Primers/genetics
MH  - Follistatin/genetics/*metabolism
MH  - Humans
MH  - Hypertrophy
MH  - Insulin-Like Growth Factor II/deficiency/genetics
MH  - Male
MH  - Mice
MH  - Mice, 129 Strain
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Muscle, Skeletal/drug effects/*metabolism/*pathology
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Receptor, IGF Type 1/genetics/*metabolism
MH  - Recombinant Proteins/genetics/metabolism
MH  - Ribosomal Protein S6 Kinases/metabolism
MH  - Signal Transduction
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors
MH  - Transfection
EDAT- 2011/11/17 06:00
MHDA- 2012/03/06 06:00
CRDT- 2011/11/17 06:00
PHST- 2011/11/17 06:00 [entrez]
PHST- 2011/11/17 06:00 [pubmed]
PHST- 2012/03/06 06:00 [medline]
AID - en.2011-1687 [pii]
AID - 10.1210/en.2011-1687 [doi]
PST - ppublish
SO  - Endocrinology. 2012 Jan;153(1):241-53. doi: 10.1210/en.2011-1687. Epub 2011 Nov 
      15.