Insulin-like growth factors and their receptors in growth.

The IGFs are essential stimulators of fetal and postnatal growth. Their signals are mediated predominantly by the type I IGF receptor, but another as yet unidentified receptor seems to mediate some actions, especially some of those for IGF-II. During organogenesis, the actions of IGF-I seem to be local (autocrine/paracrine), because it, as well as IGFBPs and IGF receptors, are expressed coordinately in a highly tissue and developmentally specific fashion. IGF-I, however, most likely assumes endocrine functions during postnatal life and provides signals for GH and nutritional status. On the other hand, IGF-II may have only local growth-promoting functions, and its most essential actions may be restricted to in utero life. Both IGFs may be involved in regenerative organ growth, and their uncontrolled expression, especially that of IGF-II, may be involved in the formation of some tumors. The previous conclusions are drawn mainly from in vitro and animal experiments. Although they are generally consistent with data in humans, it is most likely incorrect to extrapolate to man all of the conclusions drawn from the experiments in mice. Differences in placentation are so marked between mice and humans that an exclusive role for IGF-II in human placental growth seems unlikely. On the other hand, it is reasonable to conclude that both IGFs are important stimulants of normal human fetal growth, that IGF-I is a more potent stimulator of human postnatal growth, and that the type I IGF receptor mediates most IGF actions in humans. The fact that no human growth disorders have been linked convincingly to lack of function mutations in IGF or IGF receptor genes suggests that such defects are lethal.