The insulin-like growth factors and feto-placental growth.

The insulin-like growth factors, IGF-I and IGF-II, have an important role in fetoplacental growth throughout gestation. They have metabolic, mitogenic and differentiative actions in a wide range of fetal tissues including the placenta. Both Igf1and Igf2genes are expressed in fetal tissues. Expression of the Igf2gene is more abundant than Igf1 gene expression during mid to late gestation. Both IGF's are also present in the fetal circulations with 3-10 fold higher levels of IGF-II than IGF-1 during late gestation. Expression of the Igfgenes is developmentally regulated in a tissue specific manner and can be affected by nutritional and endocrine conditions in utero. Deletion of either Igfgene of the Igf1rgene retards fetal growth while over-expression of IGF-II leads to fetal overgrowth. In mice, placental growth is affected only by manipulation of the Igf2gene. The IGF's also effect the growth of individual fetal tissues and influence the uptake and utilization of nutrients by the fetal and placental tissues. Circulating concentrations and tissue expression of the IGF's are reduced by undernutrition and deficiency of nutritionally sensitive hormones, such as insulin, thyroxine and glucocorticoids. In general, the Igf1gene is more responsive to these stimuli than the Igf2gene. In addition, the effects of the IGFs on feto-placental growth can be amplified or attenuated by the IGF binding proteins, which are themselves regulated by nutritional and endocrine signals. The Igf2gene appears to provide the constitutive drive for intrauterine growth via its placental effects and direct paracrine actions on fetal tissue while the Igf1gene regulates fetal growth in relation to the nutrient supply.