Clinical relevance of systemic and local IGF-I.

The insulin-like growth factor family of ligands, receptors and binding proteins are critical for many normal physiological functions. These include normal development during fetal and post-natal development and maintenance of organ function in adult life. Circulating IGF-I is produced primarily by the liver under GH control, whereas the production of tissue IGF-I has other controls. Recent studies have demonstrated that both circulating and tissue IGF-I are important for maintaining the normal structure-function of complex organs such as bone. Circulating IGF-I is important for maintaining ambient GH levels; in its absence GH elevation is seen leading to insulin resistance. In addition, low levels of circulating IGF-I retard the progression and metastatic potential of a number of cancers.