Overview

The insulin-like growth factor axis consists of the insulin-like growth factors (IGF-I and IGF-II), the type I and type II IGF receptors, and six known IGF binding proteins (IGFBP-1 through -6). The IGFs bind both their receptors and binding proteins with high affinity. IGFs are important mitogenic factors involved in cell proliferation and metabolism. Locally produced IGFs and IGFBPs regulate tissue growth and differentiation. The IGFBPs are thought to modulate the action of IGFs in several ways, including an inhibitory model in which IGFBPs sequester IGFs from their receptors, an enhancing model in which IGFBPs transport IGFs to their site of action, or by a receptor-independent model that may involve direct interaction of IGFBPs with IGFBP receptors. IGFBPs are regulated by various endocrine factors and are expressed in specific ontogenic patterns. The degree of growth inhibition caused by the IGFBPs appears to be directly related to their concentrations relative to IGFs . The modulation of IGF levels by IGFBPs is further regulated by IGFBP proteases which cleave the high affinity IGFBPs into fragments with lower affinity for IGFs, thereby increasing free IGF bioavailability. This process leads to reduced inhibition of cell growth by IGFBPs.