PHARMACOLOGIC STUDIES OF SOY PHYTOESTROGENS

（摘自申请人摘要）在上一个项目期间，研究人员获得了实验证据，支持大豆植物雌激素（异黄酮）可能是传统激素替代疗法的有效替代，可以预防动脉粥样硬化，而不会对乳房和子宫内膜产生有害影响。研究人员还在一项针对青春期前和青春期周围食蟹雄性的研究中发现，大豆异黄酮对心脏有保护作用，对生殖系统没有影响。这些研究提高了研究者对公众健康的重要性的认识，同时对冠心病和激素依赖性癌症有潜在的保护作用。在项目1中，研究人员建议加强大豆植物雌激素的药理学研究，使用手术绝经的雌性和成熟雄性猴子进行一系列短期拉丁广场设计，以评估不同剂量、形式和植物雌激素比例对中期结果的影响（目标1,2,3）。目标4将是“最佳”（最佳蛋白质、异黄酮比例和剂量）和对照治疗的长期比较。本项目将评估治疗对女性心血管疾病危险因素、生殖系统和骨骼终点的影响。要解决的问题是：1。大豆蛋白中的高分子量部分或7S肽成分在改善脂质代谢方面是否比大豆分离蛋白更有效？异黄酮是否需要其中一个部分才能发挥作用？2. 以染料木素为主或以大豆色素为主的大豆植物雌激素制剂对疾病标志物有不同的影响吗？3. 大豆植物雌激素剂量与疾病标志物之间的关系是什么？4. 最佳大豆治疗对疾病标志物的长期影响是什么？这个项目直接关系到项目的中心主题，特别是，更好地了解大豆植物雌激素的心脏保护作用。本项目中获得的数据应有助于理解项目2和3中获得的数据，而项目2和3将提供病理结果，以支持本项目中使用的中间终点。

(Adapted from Applicant's Abstract) During the last program project period, the investigators obtained experimental evidence to support the conclusion that soy phytoestrogens (isoflavones) may be a useful alternative to traditional hormone replacement therapy for females, protecting against atherosclerosis without deleterious effects on the breast and endometrium. The investigators also found in a study with pre- and peripubertal cynomolgus males that the soy isoflavones were cardioprotective and did not affect the reproductive system. These studies increased the investigators' awareness of the public health importance of the simultaneous potential protective effects against coronary heart disease and hormone dependent cancers. In Project 1, the investigators propose to intensify their pharmacologic studies of the soy phytoestrogens using surgically menopausal female and mature male monkeys in a series of short-term Latin Square designs to assess the effects of varying doses, forms, and ratios of the phytoestrogens on intermediate outcomes (Aims 1, 2, 3). Aim 4 will be a longer-term comparison of "optimal" (best protein, isoflavone ratio, and dose) and control treatments. This project will assess treatment effects on cardiovascular disease risk factors and reproductive system of both genders and bone endpoints in females. The questions to be addressed are: 1. Is the high molecular weight fraction or the 7S peptide component in soy protein more effective than soy protein isolate on improving lipid metabolism and is one of these fractions required for the isoflavones to have their effect? 2. Are there different effects on disease markers with soy phytoestrogen preparations that are predominately genistein or predominately daidzein? 3. What is the relationship between dose of soy phytoestrogens and disease markers? 4. What are the longer-term effects of the optimal soy treatment on disease markers? This project relates directly to the central theme of the program project, specifically, to better understand the cardioprotective benefits of the soy phytoestrogens. The data to be obtained in this project should contribute to the understanding of data obtained in Projects 2 and 3 while Projects 2 and 3 will provide pathologic outcomes to support the intermediate endpoints used in this project.