PHARMACOLOGIC STUDIES OF SOY PHYTOESTROGENS

大豆植物雌激素的药理学研究

• 批准号: 2893821
• 负责人: THOMAS B CLARKSON
• 金额: $ 71.75万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-06-01 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2893821
• 关键词: Macaca fascicularis; biomarker; blood lipid; blood lipoprotein metabolism; bone metabolism; cardiovascular disorder prevention; cardiovascular pharmacology; chemoprevention; cholanate compound; cholesterol; diet therapy; dietary supplements; disease /disorder proneness /risk; dosage; female; gender difference; genistein; male; mature animal; nonhuman therapy evaluation; nutrition related tag; phytoestrogens; postmenopause; reproductive system; soybeans

We have obtained experimental evidence to support the conclusion that soy phytoestrogens may be a useful alternative to traditional hormone replacement therapy for females. We also have evidence from a study in young cynomolgus males that the soy phytoestrogens may be cardioprotective and that they do not affect the reproductive system of pre- and peripubertal males. Our concentration on postmenopausal females and soy phytoestrogens has increased our awareness of the public health importance of the simultaneous potential protective effects of soy phytoestrogens on coronary heart disease and hormone dependent cancers. That has caused us to pursue the possibility that soy phytoestrogens given to males will be cardioprotective, have no adverse effects on the reproductive system, and may provide protection against prostate cancer. We propose to intensify our pharmacologic studies of the soy phytoestrogens. We will use both postmenopausal females and males in this study in order to assess treatment effects on the cardiovascular system and reproductive system of both genders and bone metabolism biomarkers in females. This study will utilize 6 groups of 5 surgically menopausal female monkeys and 6 groups of 5 mature male monkeys assigned to a series of short-term Latin Square designs. The studies will assess the effects of varying doses, forms, and ratios of the phytoestrogens on intermediate outcomes. The specific questions to be addressed in this project are as follow: What is the peptide fraction in soy protein that is required for the isoflavones to have their effect on lipid metabolism? We will test whether the high molecular weight fraction or the 7S peptides of soy protein are required for the isoflavones to be effective. Are there differences on outcomes with soy phytoestrogen preparations that are predominately genistein or predominately daidzein? What is the relationship between dose of soy phytoestrogens (SPE) and outcomes?

我们已经获得了实验证据来支持这样的结论，即大豆植物雌激素可能是女性传统激素替代疗法的有用替代品。我们还从一项对年轻食蟹雄性的研究中获得了证据，证明大豆植物雌激素可能对心脏有保护作用，而且它们不会影响青春期前和青春期前后雄性的生殖系统。我们对绝经后女性和大豆植物雌激素的关注提高了我们对大豆植物雌激素对冠心病和激素依赖型癌症同时具有潜在保护作用的公共卫生重要性的认识。这促使我们追寻这样一种可能性，即给男性服用大豆植物雌激素对心脏有保护作用，对生殖系统没有不良影响，并可能预防前列腺癌。我们建议加强对大豆植物雌激素的药理研究。在这项研究中，我们将同时使用绝经后女性和男性，以评估性别和女性骨代谢生物标志物对心血管系统和生殖系统的治疗效果。这项研究将利用6组5只手术绝经的雌性猴子和6组5只成年雄性猴子，它们被分配到一系列短期拉丁方设计中。这些研究将评估不同剂量、形式和比例的植物雌激素对中间结果的影响。这个项目要解决的具体问题如下：大豆蛋白中的多肽成分是什么使异黄酮类化合物对脂肪代谢产生影响？我们将测试大豆蛋白中的高分子量部分或7S肽是否需要异黄酮类化合物的有效作用。以染料木素为主的大豆植物雌激素制剂和以大豆苷元为主的大豆植物雌激素制剂的结果是否存在差异？大豆植物雌激素(SPE)的剂量和结果之间有什么关系？