IGF and myostatin pathways are respectively induced during the earlier and the later stages of skeletal muscle hypertrophy induced by clenbuterol, a β₂-adrenergic agonist

Cell Biochem Funct. 2012 Dec;30(8):671-6. doi: 10.1002/cbf.2848. Epub 2012 Jun 14.

Abstract

Clenbuterol, a β₂-adrenergic agonist, increases the hypertrophy of skeletal muscle. Insulin-like growth factor (IGF) is reported to work as a potent positive regulator in the clenbuterol-induced hypertrophy of skeletal muscles. However, the precise regulatory mechanism for the hypertrophy of skeletal muscle induced by clenbuterol is unknown. Myostatin, a member of the TGFβ super family, is a negative regulator of muscle growth. The aim of the present study is to elucidate the function of myostatin and IGF in the hypertrophy of rat masseter muscle induced by clenbuterol. To investigate the function of myostatin and IGF in regulatory mechanism for the clenbuterol-induced hypertrophy of skeletal muscles, we analysed the expression of myostatin and phosphorylation levels of myostatin and IGF signaling components in the masseter muscle of rat to which clenbuterol was orally administered for 21 days. Hypertrophy of the rat masseter muscle was induced between 3 and 14 days of oral administration of clenbuterol and was terminated at 21 days. The expression of myostatin and the phosphorylation of smad2/3 were elevated at 21 days. The phosphorylation of IGF receptor 1 (IGFR1) and akt1 was elevated at 3 and 7 days. These results suggest that myostatin functions as a negative regulator in the later stages in the hypertrophy of rat masseter muscle induced by clenbuterol, whereas IGF works as a positive regulator in the earlier stages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adrenergic beta-Agonists / administration & dosage
  • Adrenergic beta-Agonists / pharmacology
  • Animals
  • Blotting, Western
  • Clenbuterol / administration & dosage
  • Clenbuterol / pharmacology*
  • Hypertrophy
  • Male
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Myostatin / metabolism*
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Rats, Wistar
  • Receptor, IGF Type 1 / metabolism
  • Signal Transduction / drug effects*
  • Smad2 Protein / metabolism
  • Smad3 Protein / metabolism
  • Somatomedins / metabolism*
  • Time Factors

Substances

  • Adrenergic beta-Agonists
  • Myostatin
  • Smad2 Protein
  • Smad3 Protein
  • Somatomedins
  • Receptor, IGF Type 1
  • Akt1 protein, rat
  • Proto-Oncogene Proteins c-akt
  • Clenbuterol