Insulin-like growth factors and their binding proteins: Biological actions

Abstract

The molecular mechanism by which IGFBPs modulate IGF action is complex. Factors such as cell surface association, ECM association, phosphorylation, or proteolysis, which alter the affinity of IGFBPs for their respective ligands, can clearly alter target cell actions. However, such conclusions are indirect and must be made with caution, since few in vivo studies exist at present. The current in vivo data are conflicting as to whether the net effect of binding proteins is inhibitory or stimulatory, although the recent IGF-I antibody studies using whole animals (326) suggest that IGFBP-3 in serum will potentiate IGF action. In contrast, IGF analog infusion studies suggest that constitutive expression of IGFBPs in some organs, such as the gut, may have a net inhibitory effect on IGF action. Gene targeting studies to delete specific IGFBP genes may be helpful in resolving these paradoxes.