The biological and structural characterization of specific serum binding proteins for the insulin-like growth factors.

The IGFs constitute an important family of skeletal growth regulatory peptides, which may play a vital autocrine and/or paracrine role in cellular growth. The role of the binding proteins in IGF physiology is quite unclear, and despite considerable progress in the past 2 years on the isolation and purification of binding proteins, many questions are still unresolved. For example, is the observed molecular heterogeneity experimentally induced, is it the result of post-translational modification of a single gene product, or are the different binding proteins products of different genes? What is the relationship between the different forms of binding proteins, and do they have different affinities for IGF-I and IGF-II? Do they have different physiological roles? It is obvious that answers to these questions are necessary in order to appreciate fully the physiological role of the binding proteins in regulating the actions of IGFs. Successful purification of different forms of IGF-binding proteins has been achieved in the last few years. This should enable the establishment of specific radioimmunoassays for each binding protein, which should allow the accurate assessment of the relative concentrations of binding proteins in various clinical or experimental states. Such studies have begun to be pursued very effectively by Baxter's group. The elucidation of the amino acid sequences of the various binding proteins will, hopefully, not only resolve the structural nature and inter-relationship of the various binding proteins, but also permit the use of recombinant DNA techniques to investigate fully, at the genetic level, the synthesis, regulation and production of the IGF-binding proteins.