Growth Hormone, Insulin-like Growth Factors and their binding proteins build up an endocrine system regulating not only longitudinal growth in humans but also influencing a broad variety of other physiological and pathophysiological processes like energy metabolism or tumor growth. Most effects of Growth Hormone (GH) are exerted by Insulin-like Growth Factors (IGF) mainly produced by liver but also locally by specific tissues. The effects of IGF are regulated, specific binding proteins (IGFBP 1-7) regulate bioavailability of IGF. After proteolytic cleavage of the binding proteins IGF is set free and able to bind to its receptor. The autophosphorylation of this thyrosine kinase receptor activates intra cellular signaling cascades. Some of these IGFBPs not only regulate the availability of IGF but also exert IGF-dependent effects on cell physiology.
IGFBP-3 is the most abundant IGFBP in circulation and therefore of special relevance in regulation of IGF effects. This is reflected by the indicative value of serum IGFBP-3 concentration in diagnostics of growth disturbances. IGFBP-3 has also been shown to be able to induce apoptosis, promote tumor growth and inhibit cellular migration and metastasis dependent on tissue and tumor stage. |
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