ENDOCRINE FUNCTIONS OF THE PLACENTA

拟议的研究解决了一般假设，在先兆子痫， 一种妊娠高血压疾病，是指 早产和胎儿生长迟缓，有异常 胎盘产生脂质过氧化物和血管活性类花生酸，和 这些异常导致了 疾病，如高血压、蛋白尿和子宫胎盘减少 血流拟议的研究解决了胎盘 前列环素（PG 1 2）（一种促排卵剂）的产生减少， 血栓素（TX），一种高血压药物，在 先兆子痫 子痫前期胎盘TX产生增加可能是 再加上胎盘过氧化脂质分泌增加。脂质 过氧化物会破坏细胞膜，因此脂质过氧化物水平升高 可能与内皮细胞损伤和PG 12减少有关。 先兆子痫胎盘将从正常妊娠女性中获得， 患有先兆子痫的女性将对胎盘组织进行孵育或灌注 在体外研究生产率、分泌率和调节 因素类二十烷酸将通过特异性放射免疫测定法测量， 通过谷胱甘肽过氧化物酶/还原酶氧化NADPH和 丙二醛生成。具体目标是确定： 人胎盘中TX和脂质过氧化物的区室化， 由滋养层控制其生产率， 正常和先兆子痫妊娠中的环氧合酶; 2）是否 羟基二十碳四烯酸（HETE）生产的区室化 胎盘可解释滋养层对胎盘血栓素的抑制; 3)胎盘血管收缩机制与失衡有关 TX和PG 12之间的关系以及脂质过氧化物水平的增加。

The proposed studies address the general hypothesis that in preeclampsia, a hypertensive disease of pregnancy that is a leading cause of indicated premature delivery and fetal growth retardation, there is abnormal placenta production of lipid peroxides and vasoactive eicosanoids, and that these abnormalities contribute to the clinical symptoms of the disorder, such as hypertension, proteinuria and reduced uteroplacental blood flow. The proposed studies address mechanisms whereby placenta production of prostacyclin (PGl2), a hypotensive agent, is decreased and that of thromboxane (TX), a hypertensive agent, is increased in preeclampsia. Increased placental TX production in preeclampsia could be coupled to an increase in placenta secretion of lipid peroxides. Lipid peroxides can damage cell membranes, so elevated levels of lipid peroxides could be related to endothelial cell injury and decreased PG12 in preeclampsia. Placentas will be obtained from normally pregnant women and women with preeclampsia. Placental tissues will be incubated or perfused in vitro to study production rates, secretion rates and regulatory factors. Eicosanoids will be measured by specific radioimmunoassays and lipid peroxides by glutathione peroxidase/reductase oxidation of NADPH and malondialdehyde generation. The specific aims are to determine: i) The compartmentalizatlon of TX and lipid peroxides in the human placenta and the control of their production rates by the trophoblast and cyclooxygenase enzyme in normal and preeclamptic pregnancies; 2) Whether compartmentalization of hydroxyeicosatetraenoic acid (HETE) production in the placenta can explain trophoblast inhibition of placental thromboxane; 3) Mechanisms for placenta vasoconstriction relating to an imbalance between TX and PG12 and increased levels of lipid peroxides.