CARDIOVASCULAR BENEFITS OF SOY PHYTOESTROGENS

拟建项目：（改编自申请人摘要）本PPG继续是一组相互关联的项目，主要关注大豆植物雌激素补充/治疗的潜在心血管益处。大豆植物雌激素（SPEs）对女性乳房和子宫以及男性前列腺的潜在益处是次要的焦点。这项研究是针对男性和绝经前和绝经后的女性。在项目1中，研究者将通过解决四个问题来加强大豆植物雌激素（spe）的药理学研究：1。植物雌激素（异黄酮）对脂质代谢有影响所需要的大豆蛋白肽部分是什么？2. 以染料木素为主或以大豆黄酮为主的大豆植物雌激素制剂的效果有差异吗？3. 大豆植物雌激素的剂量与其代谢作用有什么关系？4. “最佳”大豆治疗的长期效果是什么？项目2的主要目的是评估大豆植物雌激素在成年雄性猴子初级心脏保护中的作用。此外，该研究将直接探讨长期食用大豆是否对生殖系统、认知、社会和性行为及功能没有不利影响，并确定它是否对前列腺有有利影响。死后将评估动脉粥样硬化程度和动脉雌激素受体（α和β）的表达。此外，将研究前列腺增生和肿瘤的免疫组织化学和组织形态计量学标记，以及乳腺增生和肿瘤的组织形态计量学标记。项目3是一项综合性的围临床研究，旨在确定SPEs治疗是否能抑制冠状动脉和颈动脉粥样硬化的进展，并改善高危、隶属性绝经前猴子的冠状动脉扩张剂反应。此外，该研究将确定SPEs是否抑制或增强绝经前猴子子宫内膜和乳腺组织中的增殖和雌激素反应，以及SPEs是否对这些雌性动物的骨骼发育和骨量峰值产生不利影响或改善。

PROPOSED PROGRAM: (Adapted from Applicant's Abstract) This PPG continues to be a group of interrelated projects focused primarily on the potential cardiovascular benefits of soy phytoestrogen supplementation/treatment. Potential benefits of soy phytoestrogens (SPEs) for breast and uterus of females and of prostate of males constitute a secondary focus. The research is directed toward males and pre and postmenopausal females. In Project 1, the investigators will intensify their pharmacologic studies of the soy phytoestrogens (SPEs) by addressing four questions: 1. What is the peptide fraction of soy protein that is required for the phytoestrogens (isoflavones) to have their effect on lipid metabolism? 2. Are there differences in the effects of soy phytoestrogen preparations that are predominately genistein or predominately daidzein? 3. What is the relationship between dose of soy phytoestrogens and their metabolic effects? 4. What are the longer term effects of the "optimal" soy treatment? The major objective of Project 2 is to assess the usefulness of soy phytoestrogens in primary cardioprotection of adult male monkeys. Also, the study will address directly whether long-term soy consumption is without adverse effects on the reproductive system, cognition, social and sexual behavior and function and determine if it has favorable effects on the prostate gland. Postmortem assessments will be made of atherosclerosis extent and arterial expression of estrogen receptors (alpha and beta). In addition, immunohistochemical and histomorphometric markers of prostatic hyperplasia and neoplasia will be studied as will histomorphometric markers of mammary gland hyperplasia and neoplasia. Project 3 is a comprehensive, periclinical study that will determine whether treatment with SPEs inhibits the progression of coronary and carotid artery atherosclerosis and improves coronary artery dilator responses in high risk, subordinate premenopausal monkeys. Furthermore, the study will determine whether SPEs inhibit or potentiate proliferation and estrogenic responses in the endometrium and mammary tissue of premenopausal monkeys, and whether SPEs adversely affect or improve bone development and peak bone mass in these females.