REGULATION OF HUMAN PLACENTAL GROWTH BY IGFS

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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.