REGULATION OF HUMAN PLACENTAL GROWTH BY IGFS

人类胎盘的主要功能是确保最佳的 胎儿生长和发育的环境。 对此至关重要 作用是胎盘的程序性生长和发育。 不幸的是，我们对控制这种疾病的机制知之甚少。 胎盘生长 通过分离不同的细胞成分， 胎盘，每一个分泌的产品，可能承担的 另一个的功能可以以一种不可能的方式进行研究， 整个胎盘或胎盘细胞类型的复杂混合物。 的 拟议的研究将开发和表征模型系统 由此分子事件和细胞相互作用， 调节胎盘生长将被探索，并提供洞察力， 对正常胎儿发育很重要的机制。 胰岛素样生长因子（IGF-I和IGF-II）在胰岛素抵抗中的作用 胎盘生长和功能的调节将在 体外，使用培养的滋养层细胞和成纤维细胞来源于 人类胎盘在每个三个月作为模型系统。 每个小区 类型将被定义和表征相对于细胞- IGF生物合成、IGF受体和产生的特异性位点 IGF特异性结合蛋白 调节IGF的体液因子 合成和分泌将特别强调 胎盘因子，即绒毛膜促性腺激素（HCG）， 胎盘催乳素（hPL）。 IGFs与其他细胞相互作用 相邻的目标细胞将被研究， 通过检查IGF结合和已知的生物功能， 受IGF控制，即氨基酸和葡萄糖转运， 细胞增殖和细胞分化。 很有可能 IGFs对靶细胞电荷的生物学效应， 妊娠期作为一种特殊的细胞类型， 程序化胎盘发育 IGFs也可能发挥主要作用， 诱导细胞分化的作用。 认识到这一动态 胎盘的生长和功能方面将是必不可少的， 了解IGF表达的调控因素 胎盘发育中的生物活性及其在 调节胎盘生长

The primary function of the human placenta is to ensure an optimal environment for fetal growth and development. Essential to this role is the programmed growth and development of the placenta. Unfortunately, little is known regarding the mechanisms controlling placental growth. By isolating the different cellular elements of the placenta, the secreted products of each that may bear on the function of the other can be studied in a manner not possible with whole placentae or complex mixtures of placental cell types. The proposed studies will develop and characterize a model system whereby the molecular events and cellular interactions that regulate placental growth will be explored and provide insight into mechanisms important in normal fetal development. The role of insulin-like growth factors (IGF-I and IGF-II) in the regulation of placental growth and function will be studied in vitro, using cultured trophoblasts and fibroblasts derived from human placentae at each trimester as a model system. Each cell type will be defined and characterized with respect to cell- specific site(s) of IGF biosynthesis, IGF receptors, and production of IGF specific binding proteins. Humoral factors regulating IGF synthesis and secretion will be examined with particular emphasis on placental factors, i.e. chorionic gonadotropin (HCG) and placental lactogen (hPL). The ability of IGFs to interact with neighboring target cells will be studied in cells from each trimester by examining IGF binding and biologic functions known to be subject to IGF control, i.e. amino acid and glucose transport, cell proliferation, and cell differentiation. It is very likely that the biologic effects of the IGFs on target cells charge during gestation as a particular cell type differentiates during programmed placental development. The IGFs may also play a primary role in inducing cytodifferentiation. Recognizing this dynamic aspect of placental growth and function will be essential to understanding the factors regulating the expression of IGF bioactivity in the developing placenta and the role it plays in regulating placental growth.