Normal progression of growth and maturation of the fetus requires concomitant maternal metabolic adjustments. Trophoblast cells and their secretory products provide the signalling system that coordinates the activities of fetal and maternal tissues. At present, our understanding of the trophoblast signalling system is poor. The goal of this research is to further our understanding of an important family of regulatory proteins produced by trophoblast cells. These placental proteins are all structurally related to pituitary prolactin (PRL). We hypothesize that this family of placental proteins is involved in directing the physiological adaptations of maternal and fetal tissues that occur during pregnancy in the rat. In the rat, a total of six distinct members of the placental PRL family have been identified and partially characterized. The biological actions of four members, PRL-like protein-A (PLP-A), PLP-B, PLP-C, and placental lactogen-I variant (PL-Iv) are unknown. These four proteins are synthesized in abundant amounts and represent the major placental secretory proteins of the second half of pregnancy. Specifically, we propose to: 1) generate and characterize recombinant PLP- A, PLP-B, PLP-C, and PL-Iv proteins; 2) examine the distribution of PLP-A, PLP-B, PLP-C, and PL-Iv in maternal, fetal, and amniotic compartments; 3) evaluate the PRL- and GH-like biological activities of PLP-A, PLP-B, PLP-C, and PL-Iv. Molecular biology, protein chemistry, immunochemistry and cell culture techniques will be used to elucidate the biological activities of these four members of the placental PRL gene family. It is important to appreciate that disruptions in the coordination of fetal and maternal activities are potential causes of abnormal development. Thus, the inappropriate expression or action of members of the placental PRL family may have significant consequences on embryonic/fetal development.
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