Clinical significance of insulin-like growth factor binding proteins (IGFBPs)

The insulin-like growth factors (IGFs) are potent mitogenic agents involved in the regulation of somatic growth and cellular proliferation. Recently, the complex milieu in which they operate has begun to be unraveled. Endocrine and autocrine patterns of IGF secretion have been identified and specific cell surface receptors that bind IGFs and mediate their biological actions have been characterized. The IGF binding proteins (IGFBPs), a family of six peptides that bind IGFs with high affinity (thus regulating IGF availability to its receptors), have been recognized as a new class of growth modulators. The IGFBPs can inhibit IGF actions, enhance the mitogenic effects of IGFs, or function as independent cell regulatory factors, possibly by interacting with their own receptors on the cell membrane. The IGFBPs, in turn, are regulated by the IGFBP proteases, a group of proteolytic enzymes that are capable of cleaving IGFBPs into smaller fragments with lower affinity for the IGFs, thus enhancing IGF action. The six IGFBPs, while similar, have unique biological properties and appear to have specific patterns of expression and function. Radioimmunoassays for IGFBP-1, −2, and −3 are currently commercially available and information is accumulating on their diagnostic usefulness. This includes several clinical situations, such as growth disorders, where serum IGFBP-3 is a highly specific screening tool for growth hormone deficiency, various malignancies in which serum IGFBP-2 levels are elevated, and disorders of carbohydrate metabolism that display an inverse relationship between serum IGFBP-1 and insulin secretion. Current clinical practice may include the judicious use of these tests for the diagnosis and for monitoring the therapeutic response of such disorders.