THE IMPORTANCE OF UDP-GLUCURONOSYLTRANSFERASE ENZYMES IN PREGNANCY AND EMBRYOGEN

UDP-葡萄糖醛酸基转移酶在妊娠和胚胎时期的重要性

• 批准号: 8167757
• 负责人: Abby Cherise Collier
• 金额: $ 20.7万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167757
• 关键词: Adult; Assisted Reproductive Technology; Biological; Chemicals; Computer Retrieval of Information on Scientific Projects Database; Enzymes; Family; Fetal Development; First Pregnancy Trimester; Funding; Glucuronosyltransferase; Goals; Grant; Hand; Hormones; Human; Human Development; Institution; Liver; Metabolic; Modeling; Mus; Pharmaceutical Preparations; Placenta; Play; Pregnancy; Process; Protein Isoforms; Reproduction; Research; Research Personnel; Resources; Role; Source; Testing; Transferase; UGT1A1 gene; United States National Institutes of Health; environmental chemical; steroid metabolism

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The superfamily of UDP-glucuronosyl transferase (UGT) enzymes are critical for the metabolic clearance of most biological substances including chemicals, hormones, dietary drugs and environmental chemicals. They regulate the levels of these compounds by degrading them. We have previously demonstrated that UGTs play an important role in human reproduction. During the first trimester of pregnancy, total UGT activity in the human placenta is equal to or greater than that found in the liver of adults. This incredibly high rate of activity in the placenta suggests that some isoforms in the superfamily play key roles in pregnancy and human development. Two sub-families exist: UGT1A and UGT2B and we have previously demonstrated that UGT2B isoforms are present in relatively low levels and static. On the other hand, UGT1A levels are higher and dynamic during pregnancy. Taken together, these facts strongly support that UGT enzymes, especially those in the UGTA1 subfamily, are important in pregnancy and fetal development. However, their precise role in this process remains unclear. The major goal of this Project is to understand the role of UGT enzymes in normal pregnancy. This will be accomplished by testing UGT levels in normal and abnormal human placentas. We will also determine how UGT alters steroid metabolism in assisted reproductive technologies using the mouse as a model.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 中心，不一定是研究者的机构。 UDP-葡萄糖醛酸基转移酶 (UGT) 超家族对于大多数生物物质（包括化学品、激素、膳食药物和环境化学品）的代谢清除至关重要。它们通过降解这些化合物来调节它们的水平。 我们之前已经证明 UGT 在人类生殖中发挥着重要作用。 在怀孕的前三个月，人类胎盘中的总 UGT 活性等于或大于成人肝脏中的 UGT 活性。 胎盘中这种令人难以置信的高活性表明该超家族中的一些亚型在妊娠和人类发育中发挥着关键作用。 存在两个亚家族：UGT1A 和 UGT2B，我们之前已经证明 UGT2B 亚型以相对较低的水平且静态存在。 另一方面，怀孕期间 UGT1A 水平较高且动态。 总而言之，这些事实有力地支持 UGT 酶，尤其是 UGTA1 亚家族中的酶，对于妊娠和胎儿发育非常重要。 然而，它们在此过程中的确切作用仍不清楚。 该项目的主要目标是了解 UGT 酶在正常妊娠中的作用。 这将通过测试正常和异常人类胎盘中的 UGT 水平来实现。 我们还将以小鼠为模型，确定 UGT 如何改变辅助生殖技术中的类固醇代谢。