EFFECT OF NOVEL ANDROGENS ON ECTOPIC ENDOMETRIUM IN RHESUS MACAQUES

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 目的是研究新的药物治疗子宫内膜异位症。 猕猴子宫内膜可以自体移植到异位的腹腔内和皮下部位。 这些子宫内膜移植物为新型抗子宫内膜异位疗法的临床前试验提供了一个极好的子宫内膜异位样模型系统。 拜耳先灵制药股份公司（BSP）正在开发一种睾酮类似物（eF-MENT），它比睾酮具有更高的雄激素活性，并且不会被肝脏和脂肪组织转化为睾酮等雌激素。 在这项研究中，我们将测试EF-MENT对雌激素刺激的子宫内膜移植物生长的影响，并将EF-MENT的影响与作为阳性对照的双氢睾酮（DHT，一种天然雄激素）的影响进行比较。 这项研究有两个目的：目的1是开发方法，以确定雄激素在雌性猕猴中的非生殖“脱靶”效应，类似于女性雄激素治疗的副作用。 目的2是确定eF-MENT治疗是否会抑制恒河猴异位子宫内膜的生长。目前正在进行eF-MENT通过干燥剂植入给药的剂量探索研究。我们确定了一种不会导致脱靶作用的植入剂量，并将其与导致非靶效应的剂量进行了比较。 所有剂量的eF-MENT均抑制了动物的异位子宫内膜。 相反，只有高剂量的DHT植入抑制移植物生长。 我们建议，eF-MENT可以开发作为一种治疗妇女子宫内膜异位症。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The goal is to investigate new drug therapies for endometriosis. Macaque uterine endometrium can be auto-transplanted to ectopic intra-abdominal and subcutaneous sites. These endometrial grafts provide an excellent endometriosis-like model system for preclinical testing of novel anti-endometriotic therapies. Bayer Schering Pharma AG (BSP) is developing a testosterone analog (eF-MENT) that exerts higher androgenic activity than testosterone and is not converted to estrogens like testosterone by the liver and fat tissues. In this study we will test the effect of eF-MENT on estrogen-stimulated growth in endometrial grafts, and compare the effects of eF-MENT with the effects of dihydrotestosterone (DHT a natural androgen) as a positive control. This study had two aims: Aim 1 is to develop methods to identify nonreproductive "off-target" effects of androgens in female macaques that are analogous to the side effects of androgen therapy in women. Aim 2 is to determine if eF-MENT therapy will inhibit growth in ectopic endometrium in rhesus macaques. Dose finding studies, with eF-MENT administered by siclastic implant, are underway. We identified a implant dose that resulted in no off-target actions and compared it to doses that resulted in non-target effects. All doses of eF-MENT resulted in suppression of ectopic endometrium in the animals. In contrast only the high dose DHT implants suppress graft growth. We propose that eF-MENT can be developed as a therapy for endometriosis in women.