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Am J Physiol Endocrinol Metab 282: E31-E37, 2002;
0193-1849/02 $5.00
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Vol. 282, Issue 1, E31-E37, January 2002

Role of IGF-I and IGFBPs in the changes of mass and phenotype induced in rat soleus muscle by clenbuterol

Bonaventure L. Awede1, Jean-Paul Thissen2, and Jean Lebacq1

1 Unité de Physiologie Générale des Muscles, and 2 Unité de Diabétologie et Nutrition, Université Catholique de Louvain, 1200 Brussels, Belgium

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.

insulin-like growth factor; insulin-like growth factor-binding proteins; beta 2-adrenoceptor agonists; hypertrophy; fiber type


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