Regulation of type 1 insulin-like growth factor (IGF) receptors and IGF-I mRNA by age and nutrition in ovine skeletal muscles

Abstract

The relative abundance and location of type 1 IGF receptors in sheep muscles have been measured to determine whether changes occur during post-natal growth and nutritional stress. Using the technique of histological autoradiography, specific binding of 125I-IGF-I in muscle fibre and connective tissue of M. biceps femoris and M. gastrocnemius was demonstrated, as was specific binding to the tendon of M. gastrocnemius and the surrounding connective tissue. The binding site in both muscles was characterised as the type 1 IGF receptor in membrane preparations using competitive binding assay and SDS-PAGE. Type 1 receptors were more abundant in connective tissue than muscle fibre or tendon (P < or = 0.001). Levels changed significantly with age in all tissues (P = 0.054 to P < or = 0.001), while change as a result of fasting was limited to a receptor increase in the connective tissue of M. gastrocnemius (P = 0.034). IGF-I mRNA in M. biceps femoris, as assessed by in situ hybridisation, showed changes in expression with increasing age (P < or = 0.025) but no change with fasting. These data indicate that the distribution, relative abundance and nutritional sensitivity of type 1 receptors are related to cell type in vivo. The overall decline of receptors with increasing age may be a feature of transition from linear animal growth to cell maintenance in adult animals. Connective tissue appears to be more sensitive than muscle fibre to nutrition, possibly allowing the reduction of non-essential metabolism during fasting.