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The yin and the yang of the IGF system: immunological manifestations of GH resistance

The insulin-like growth factors (IGFs) are widely expressed and modulate the activity of most functions in the body (1). Circulating (endocrine) IGF-I is synthesized in the liver in response to growth hormone (GH) acting through GH receptors on the cell surface of hepatocytes. This endocrine IGF-I mediates longitudinal growth during childhood and puberty, and regulates protein synthesis in muscle throughout life. Locally produced IGFs act via autocrine/paracrine modes on the tissues from which they are released and regulate cellular proliferation. In addition to the IGFs, tissues produce six different IGF-binding proteins (IGFBPs) which form various complexes with IGFs in the circulation and in extracellular fluids and modulate their activity. While the IGFBPs are important components of this growth factor/hormone system, the final effects of IGFs on target tissues are mediated by the IGF-I receptor (2, 3). The levels of the IGF-I receptor in different tissues are regulated by specific factors