CLINICAL-SIGNIFICANCE OF INSULIN-LIKE GROWTH-FACTOR BINDING-PROTEINS (IGFBPS)

The insulin-like growth factors (IGFs) are potent mitogenic agents inv olved in the regulation of somatic growth and cellular proliferation. Recently, the complex milieu in which they operate has begun to be unr aveled. Endocrine and autocrine patterns of IGF secretion have been id entified and specific cell surface receptors that bind IGFs and mediat e their biological actions have been characterized. The IGF binding pr oteins (IGFBPs), a family of six peptides that bind IGFs with high aff inity (thus regulating IGF availability to its receptors), have been r ecognized as a new class of growth modulators. The IGFBPs can inhibit IGF actions, enhance the mitogenic effects of IGFs, or function as ind ependent cell regulatory factors, possibly by interacting with their o wn receptors on the cell membrane. The IGFBPs, in turn, are regulated by the IGFBP proteases, a group of proteolytic enzymes that are capabl e of cleaving IGFBPs into smaller fragments with lower affinity for th e IGFs, thus enhancing IGF action.The six IGFBPs, while similar, have unique biological properties and appear to have specific patterns of e xpression and function. Radioimmunoassays for IGFBP-1, -2, and -3 are currently commercially available and information is accumulating on th eir diagnostic usefulness. This includes several clinical situations, such as growth disorders, where serum IGFBP-3 is a highly specific scr eening tool for growth hormone deficiency, various malignancies in whi ch serum IGFBP-2 levels are elevated, and disorders of carbohydrate me tabolism that display an inverse relationship between serum IGFBP-1 an d insulin secretion. Current: clinical practice may include the judici ous use of these tests for the diagnosis and for monitoring the therap eutic response of such disorders.