EFFECT OF NOVEL ANDROGENS ON ECTOPIC ENDOMETRIUM IN RHESUS MACAQUES

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 其目标是研究治疗子宫内膜异位症的新药疗法。猕猴子宫内膜可以自体移植到异位的腹内和皮下。这些子宫内膜移植物为抗子宫内膜异位症新疗法的临床前测试提供了一个很好的类似子宫内膜异位症的模型系统。拜耳先灵制药公司(BSP)正在开发一种睾酮类似物(EF-ment)，这种类似物比睾酮具有更高的雄激素活性，而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对雌激素刺激的子宫内膜移植物生长的影响，并将其与双氢睾酮(DHT)作为阳性对照进行比较。这项研究有两个目标：目标1是开发方法来确定雄激素在雌性猕猴体内的非生殖“非靶标”效应，这些效应类似于雄激素治疗对雌性猕猴的副作用。目的2是确定EF治疗是否会抑制恒河猴异位内膜的生长。剂量发现研究正在进行中，通过硅胶植入物进行治疗。我们确定了一种不会导致非靶点作用的植入剂量，并将其与导致非靶点效应的剂量进行了比较。不同剂量的EF均能抑制动物异位内膜。相反，只有大剂量的DHT植入物会抑制移植物生长。我们建议EFET可以作为治疗女性子宫内膜异位症的一种方法。

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.