AUTOIMMUNE OVARIAN FAILURE

拟议研究的目标是检测和评估卵巢 卵巢早衰患者血清抗体(OVA)的检测 描述过继抗原的特征，并检查几种动物模型 类似自身免疫性POF的过程使实验更加广泛 可以进行研究。该项目的次要成果将是 接受治疗的妇女的卵清蛋白和卵清蛋白含量的常规诊断分析 反转POF的理论。 将对诊断为POF的患者的血清进行抗体筛查 以获取有关人类卵巢组织的病史和 卵泡刺激性不孕症患者的频率，建立一种快速的方法 筛选卵清蛋白并获得卵清蛋白以用于进一步抗原研究 网站。 参与卵巢自身免疫反应的抗原将是 以逐渐更具体地测试OVA与 人类卵巢组织。抗原将通过光和电子来识别 显微免疫细胞化学，卵巢提取物的蛋白质印迹分析， 培养中颗粒细胞活性的调节及其与颗粒细胞的相互作用 促性腺激素受体。此外，我们还将研究卵清蛋白的相互作用 与其他激素性内分泌组织(肾上腺和胎盘)一起用于 与Addison病相关抗原位点的比较。目的 这些研究中的一项是确定涉及到的抗原类型 自身免疫性卵巢早衰，评估它们在卵巢功能中的作用，并确定 卵清蛋白与卵巢细胞的相互作用是卵巢减少的基础 功能。 自身免疫，特别是内分泌自身免疫的动物模型 将极大地促进我们对 这些疾病的发展。我们计划调查几个潜在的 自身免疫性卵巢早衰的动物模型与人类相似 用作研究自身免疫过程的模型系统： (1)第3天切除胸腺的小鼠，显示卵巢停滞 发育及相关卵泡蛋白，(2)卵巢主动免疫大鼠 细胞和(3)注射抗T细胞单抗的小鼠 抑制因素。

The goals of the proposed studies are to detect and assess ovarian antibodies (OVA) in patients with premature overian failure (POF), characterize the overian antigens and examine several animal models for a similar process of autoimmune POF so that more extensive experimental studies can be conducted. A secondary outcome of this project will be routine diagnostic assays for OVA and for OVA content in women receiving theorapy for reversal of POF. The serum from patients with diagnosed POF will be screened for antibodies to human ovarian tissue in order to obtain information on the history and frequency of infertility patients with OVA, establish a rapid method of screening serum for OVA and to obtain OVA for further studies of antigenic sites. The antigens involved in the autoimmune response to the ovary will be characterized in progressively more specific tests of OVA interaction with human ovarian tissue. Antigens will be identified by light and electron microscopic immunocytochemistry, Western blot analysis of ovarian extracts, modification of granulosa cell activity in culture and interaction with gonadotropin receptors. Furthermore, we will examine interaction of OVA with other steroidogenic endocrine tissue (adrenal and placenta) for comparison with antigenic sites involved in Addison's disease. The purpose of these studies is to identify the types of antigens involved in autoimmune POF, assess their role in ovarin function and determine if the interactiion of OVA with ovarian cells is a basis for reduced ovarian function. Animal models of autoimmunity and in particular of endocrine autoimmunity would greatly facilitate our understanding of the process involved in development of these diseases. We plan to investigate several potential animal models of autoimmune POF for OVA similar to those found in humans for use as model systems in which to examine the process of autoimmunity: (1) day 3 thymectomized mice that were shown to have arrested ovarian development and associated OVA, (2) rats actively immunized with ovarian cells and (3) mice injected with monoclonal antibodies to T-cell derived suppressor factors.