PRECLINICAL STUDIES ON NONHUMAN PRIMATE ENDOMETRIAL XENOGRAFTS

非人灵长类子宫内膜异种移植物的临床前研究

• 批准号: 8173215
• 负责人: OV D SLAYDEN
• 金额: $ 9.51万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8173215
• 关键词: Agonist; Computer Retrieval of Information on Scientific Projects Database; Conduct Clinical Trials; Endometrial; Endometrium; Estradiol; Estrogen Antagonists; Estrogen Receptor Modulators; Estrogen Receptor alpha; Estrogen Receptor beta; Estrogen Receptors; Funding; Generations; Goals; Grant; Growth; Institution; Lesion; Macaca; Mediating; Modeling; Mus; Primates; Progesterone; Reporting; Research; Research Personnel; Resources; SCID Mice; Safety; Site; Source; Testing; Tissues; Transplantation; United States National Institutes of Health; Uterus; Woman; Xenograft Model; Xenograft procedure; endometriosis; inhibitor/antagonist; nonhuman primate; preclinical study; response

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. Endometriosis is a condition where endometrium-like tissue forms lesions at sites outside the uterus. Our goal is to test potential therapies for endometriosis. To do this we have developed a model in which we transplant macaque endometrium into immunodeficient SCID mice, which are incapable of rejecting xenografts. The endometrial xenografts grow in response to estradiol (E2) and undergo cyclic breakdown similar to endometriosis in women. Recent studies indicate estrogen receptor (ER) alpha mediates the proliferative effects of E2 in endometriosis and that ER beta could act as an inhibitor of ER alpha action. Other studies indicate that progesterone antagonists (PA) also block E2 stimulated endometrial growth. Our aim in this study was to assess the safety and efficacy of ER beta agonist therapy and progesterone antagonist therapy for in our xenograft model prior to conducting clinical trials on endometriosis in women. We compared the effects of two ER beta agonists, a potent antiestrogen (ER beta plus ER alpha antagonist) and a new generation PA on E2 stimulated growth in ectopic endometrium. We report that both the ER antagonist, and PA blocked E2 stimulated growth of ectopic primate endometrium in the mice. However, ER beta agonists had no effect on endometrial xenograft growth.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 子宫内膜异位症是一种子宫内膜样组织在子宫外部位形成病变的疾病。 我们的目标是测试子宫内膜异位症的潜在疗法。 为此，我们开发了一种模型，将猕猴子宫内膜移植到免疫缺陷的 SCID小鼠，其不能排斥异种移植物。 子宫内膜异种移植物对雌二醇（E2）有反应，并经历类似于女性子宫内膜异位症的周期性分解。 最近的研究表明，雌激素受体（ER）α介导E2在子宫内膜异位症中的增殖作用，ER β可作为ER α作用的抑制剂。 其他研究表明，孕酮拮抗剂（PA）也阻断E2刺激的子宫内膜生长。 本研究的目的是在对女性子宫内膜异位症进行临床试验之前，评估ER β激动剂治疗和孕酮拮抗剂治疗在异种移植模型中的安全性和有效性。 我们比较了两种ER β激动剂，一种强效抗雌激素（ER β + ER α拮抗剂）和新一代PA对E2刺激的异位子宫内膜生长的影响。 我们报告，雌激素受体拮抗剂，PA阻断E2刺激的小鼠异位灵长类动物子宫内膜的生长。 然而，ER β激动剂对子宫内膜异种移植物的生长没有影响。