PRECLINICAL STUDIES ON NONHUMAN PRIMATE ENDOMETRIAL XENOGRAFTS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 子宫内膜异位症是子宫内膜样组织在子宫外部位形成病变的一种情况。我们的目标是测试治疗子宫内膜异位症的潜在疗法。为此，我们开发了一种模型，在该模型中，我们将猕猴子宫内膜移植到免疫缺陷 不能排斥异种移植的SCID小鼠。异种子宫内膜移植对雌二醇(E_2)的反应而生长，并经历类似于女性子宫内膜异位症的周期破裂。最近的研究表明，雌激素受体(ER)α介导了E2在子宫内膜异位症中的增殖作用，而ERβ可能是ERα作用的抑制因子。其他研究表明，孕激素拮抗剂(PA)也能阻断E2刺激的子宫内膜生长。我们在这项研究中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ERβ激动剂治疗和孕酮拮抗剂治疗在我们的异种移植模型中的安全性和有效性。我们比较了两种ERβ激动剂，一种有效的抗雌激素药物(ERβ加ERα拮抗剂)和新一代PA对E2刺激异位内膜生长的作用。我们报道了ER拮抗剂和PA阻断E2刺激小鼠异位灵长类子宫内膜的生长。然而，ERβ激动剂对异种子宫内膜移植的生长没有影响。

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.