The objectives of this research are to define, in the human fetus, amniotic fluid, fetal membranes, and decidua vera, events that constitute a metabolic communication system and to identify those fetal maturatinal processes that initiate parturition. The goals of Project I are to identify and characterize the key enzymes in fetal membranes and decidual tissues that catalyze reactions leading to the release of arachidonic acid from specific glycerophospholipids. The mechanism(s) for the regulation of these reactions will be investigated. Special emphasis will be placed on the role of Ca++ and Ca++ plus calmodulin in the activation of phospholipase A2 and phosphatidlinositol-specific phospholipase C. The role of regulatory proteins, e.g., lipomodulin, and the phosphorylation of lipomodulin, in arachidonic acid release will be investigated. The goals of Project II are to define the specific prostanoids that are synthesized by the uterine and intrauterine tissues as reflected by the concentrations of these prostanoids in the amniotic fluid and the maternal circulation and identify the tissue site of origin of the prostanoids produced in increased amounts during human labor. We will ascertain whether the increase in prostanoid synthesis with parturitionprecedes or only accompanies the onset of labor. The goals of Project III are to develop and refine in vitro model systems for the investigation of interrelationships between various uterine and intrauterin tissues. We will use these model systems to identify the putative signal for the initiation of parturition and the mechanism(s) by which this signal is propagated to the myometrium. The roleof adenylate cyclase activity as well as Alpha-and Beta-adrenergic and dopaminergic receptor-mediated phenomena in fetal membranes and decidua in the initiationof labor will be investigated. The goals of Project IV are to investigate, at the molecular level, the regulation of steroidogenesis and growth of the human fetal adrenal and to identify the metabolic processes influenced by secretions of the adrenal that relate to the initiation of parturition. In particular, we will seek to seek to establish whether a growth factor exists that, in concert with ACTH, stimulates the development of the fetal zone. The goals of Project V are to investigate the neuroendocrine events that culminate in the maturation of the processing of the pro-opiocortin molecule and to evaluate the role of derivatives of pro-opiocortin in the growth and steroidogenic capacity of the fetal adrenal.
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