Inhibition of the Insulin-Like Growth Factor (IGF)–IGF-Binding Protein Interaction

A family of six insulin-like growth factor (IGF) binding proteins transport IGFs in the circulation and regulate their extravascular distribution. The acid-labile subunit (ALS) combines with IGF-binding protein (IGFBP)-3 or IGFBP-5 to form abundant and stable heterotrimeric IGF-transporting complexes which are confined to the circulation. The factors that determine ALS dissociation, and regulate IGF and IGFBP passage out of the circulation, are poorly understood. Binary IGF-IGFBP complexes have high affinities and slow dissociation rates, which may be accelerated by partial IGFBP proteolysis and interaction with glycosaminoglycans. IGFBPs can interfere in IGF analyses, so removal of IGFBPs, and minimization of their influence in IGF assays, is essential to ensure valid quantification of IGFs.