The Insulin-Like Growth Factors

The recent availability of reagents to study the IGFs, their receptors, and binding proteins has led to an explosive growth in the study of IGF physiology. However, most studies to date have been descriptive, and studies delineating mechanisms of action are limited. It is apparent that most organ systems synthesize several components of the IGF system necessary for IGF to function in an autocrine or paracrine fashion and that regulation of this system occurs at the local level. However, the relative importance of locally produced IGF vs circulating IGF remains unclear. The mechanisms by which the IGFBPs modulate IGF activity are crucial to understanding this system, and identification of specific roles for each of these proteins will be required. Of critical importance is the identity of the intracellular signal transduction system by which the IGF receptor mediates the effects of the IGFs, and the delineation of mechanisms by which the IGFBPs interact with the receptor at the cellular level. It is also of interest to determine what role, if any, the IGF-II receptor plays in mediating the growth-promoting effects of the IGFs. The ubiquitous distribution of the IGFs, IGFBPs, and IGF receptors indicates that they may play a role in the regulation of coordinate growth among several tissues and cell types. Understanding the mechanisms by which these components interact to coordinate growth responses between different cell types should greatly enhance our understanding of normal growth and development.