The overall objective of this proposal is to extend our investigations of the regulation of the synthesis and release of prolactin from human decidual tissue from normal pre-term and term pregnancies and from pregnancies complicated by diabetes mellitus, pre-eclampsia, polyhydramnios and other pathologic conditions. During the past few years, we have demonstrated that the regulation of the synthesis and release of decidual prolactin differs from that of pituitary prolactin. Both the synthesis and release of decidual prolactin appear to be primarily under "local control, stimulated by a peptide released by the placenta and inhibited by arachidonic acid and by the peptide released by the decidua. The specific aims of the proposal are to (1) isolate and characterize the placental and decidual peptides which affect the release of decidual prolactin and develop radioimmunoassays for their detection, (2) study the effects of the peptides on the synthesis and release of prolactin from decidual explants from normal and pathologic pregnancies at various stages of gestation, (3) investigate the effects of progesterone, estrogen, prostaglandin and other factors on the synthesis and release of the two peptides at various stages of gestation, (4) determine the number and affinity of decidual binding sites for the peptides during pregnancy, and (5) examine the effects of the peptides on cyclic AMP levels, phospholipase A2 activity, the phosphatidylinositol cycle and calcium flux in an enriched fraction of decidual cells which synthesize and release prolactin. Since studies indicate that decidual tissue is the source of the large quantities of prolactin in amniotic fluid, these investigations should provide insight into the regulation of amniotic fluid prolactin in normal and pathologic pregnancies. Such investigations are of clinical importance since amniotic fluid prolactin appears to have many important physiologic actions, including regulation of the ion and water content of amniotic fluid.