Fowden Abigail L
Department of Physiology, University of Cambridge, CB2 3EG Cambridge, UK.
Placenta. 2003 Sep-Oct;24(8-9):803-12. doi: 10.1016/s0143-4004(03)00080-8.
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.
胰岛素样生长因子IGF-I和IGF-II在整个妊娠期的胎儿-胎盘生长中发挥着重要作用。它们在包括胎盘在内的多种胎儿组织中具有代谢、促有丝分裂和分化作用。Igf1和Igf2基因均在胎儿组织中表达。在妊娠中期至晚期，Igf2基因的表达比Igf1基因更为丰富。两种IGF在胎儿循环中也均有存在，在妊娠晚期，IGF-II的水平比IGF-1高3至10倍。Igf基因的表达以组织特异性方式受到发育调控，并且可能受子宫内营养和内分泌状况的影响。Igf基因或Igf1r基因的缺失会阻碍胎儿生长，而IGF-II的过表达则会导致胎儿过度生长。在小鼠中，胎盘生长仅受Igf2基因操作的影响。IGF还影响单个胎儿组织的生长，并影响胎儿和胎盘组织对营养物质的摄取和利用。营养不足以及胰岛素、甲状腺素和糖皮质激素等营养敏感激素缺乏会降低IGF的循环浓度和组织表达。一般而言，Igf1基因对这些刺激的反应比Igf2基因更敏感。此外，IGF结合蛋白可放大或减弱IGF对胎儿-胎盘生长的影响，而IGF结合蛋白本身也受营养和内分泌信号的调控。Igf2基因似乎通过其胎盘效应以及对胎儿组织的直接旁分泌作用为子宫内生长提供组成性驱动力，而Igf1基因则根据营养供应情况调节胎儿生长。
