From animal to molecule: aspects of the biology of insulin-like growth factors.

The synthesis of IGF-II mRNA in sheep foetal tissues is considerably higher than IGF-I. IGF-II probably has a paracrine role in the foetus; however it is likely that IGF-I originates mainly from the foetal liver and has an endocrine function. Although in the adult system IGF-I is tightly bound to serum carrier proteins it is potentially biologically active. Galactopoiesis in the goat mammary gland provides a useful model for demonstrating the importance of circulating IGF-I as a mediator of GH action. Ligand-receptor interactions involved in the stimulation of Swiss 3T3 fibroblasts by IGF-I, II and insulin were examined. It was found that the potency of binding to type I receptors was IGF-I greater than IGF-II much greater than insulin by competitive binding assays and chemical cross-linking studies, and that some cell lines secrete an IGF binding protein which is specific for IGF-I and II and which acts as an inhibitor in cellular binding assays. Maximal stimulation of DNA synthesis induced by IGF-I, II and insulin in the presence of synergising mitogens were similar. While the actions of the IGFs were consistent with type I receptor binding insulin appeared to act through its own receptor. The reduction of EGF receptor affinity following the addition of IGF-I and insulin to 3T3 cells may involve a protein kinase that is not sensitive to phorbol esters. 3T3 cell nuclei contain endogenous inositol phospholipids and their corresponding kinases and monoesterases.(ABSTRACT TRUNCATED AT 250 WORDS)