Role of IGF-I and IGFBPs in the changes of mass and phenotype induced in rat soleus muscle by clenbuterol.
Clenbuterol induces hypertrophy and a slow-to-fast phenotype change in skeletal muscle, but the signaling mechanisms remain unclear. We hypothesized that clenbuterol could act via local expression of insulin-like growth factor I (IGF-I). Administration of clenbuterol to 3-mo-old female Wistar rats resulted in a 10 and 13% increase of soleus muscle mass after 3 and 9 days, respectively, reaching 16% after 4 wk. When associated with triiodothyronine, clenbuterol induced a dramatic slow-to-fast phenotype change. In parallel, clenbuterol administration induced in soleus muscle a fivefold increase in IGF-I mRNA levels associated with an eightfold increase in IGF-binding protein (IGFBP)-4 and a fivefold increase of IGFBP-5 mRNA levels on day 3. This increased IGF-I gene expression was associated with an increase in muscle IGF-I content, already detected on day 1 and persisting until day 5 without increase in serum IGF-I concentrations. These data show that muscle hypertrophy induced by clenbuterol is associated with a local increase in muscle IGF-I content. They suggest that clenbuterol-induced muscle hypertrophy could be mediated by local production of IGF-I.
Awede
Bonaventure L
BL
Unité de Physiologie Générale des Muscles, Université Catholique de Louvain, 1200 Brussels, Belgium.
Thissen
Jean-Paul
JP
Lebacq
Jean
J
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001769:Blood / Q000378:metabolism; D002976:Clenbuterol / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000235:genetics / Q000378:metabolism; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000235:genetics / Q000378:metabolism; D018969:Insulin-Like Growth Factor Binding Proteins / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007527:Isoenzymes / Q000378:metabolism; D018482:Muscle, Skeletal / Q000033:anatomy & histology* / Q000187:drug effects / Q000502:physiology*; D018995:Myosin Heavy Chains / Q000378:metabolism; D009929:Organ Size / Q000502:physiology; D010446:Peptide Fragments / Q000378:metabolism; D010641:Phenotype; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D018974:Insulin-Like Growth Factor Binding Protein 4; D018975:Insulin-Like Growth Factor Binding Protein 5; D018969:Insulin-Like Growth Factor Binding Proteins; D007527:Isoenzymes; D010446:Peptide Fragments; D007334:Insulin-Like Growth Factor I; D018995:Myosin Heavy Chains; D002976:Clenbuterol