SOY AND ESTROGEN INTERACTIONS IN THE BREAST

大豆和雌激素在乳房中的相互作用

• 批准号: 6866872
• 负责人: J. MARK CLINE
• 金额: $ 52.64万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6866872
• 关键词: Macaca fascicularis; alternative medicine; animal puberty; biopsy; cancer prevention; cell differentiation; cell proliferation; developmental genetics; dietary constituent; endocrinology; estrogens; female; functional /structural genomics; gene environment interaction; gene expression; gene expression profiling; gonadotropins; hormone regulation /control mechanism; longitudinal animal study; mammary epithelium; mammary gland; menstrual cycle; nutrient interaction; nutrition aspect of cancer; reproductive development; serology /serodiagnosis; sex hormones; soybeans

DESCRIPTION (provided by applicant): Dietary soy consumption has been associated with decreased breast cancer risk in demographic and observational studies in women, and the protective effects appear to be stronger when soy is consumed earlier in life. Rodent studies have demonstrated profound protective effects for animals exposed early in life to soy isoflavones. Our data in the postmenopausal monkey model clearly show antiproliferative effects of soy consumption on the breast, and we have also observed that soy consumption reduces estrogen exposure of the breast. We have demonstrated the predictive value of the monkey model for breast cancer risk in the postmenopausal setting, and we believe that the model is particularly applicable to studies of pubertal breast development, which is difficult to study in human patients. We hypothesize that dietary soy consumption during puberty reduces breast proliferation, induces breast differentiation, and reduces hormonal exposure to the developing breast; such an effect would explain the observed lower risk of breast cancer in women and animals exposed to soy diets early in life. To test this hypothesis, we propose to randomize 40 pre-pubertal female cynomolgus monkeys to receive either a high-soy diet (modeling a soy-supplemented diet) or no dietary soy (modeling a typical North American diet), and to follow them longitudinally through the course of menarche and pubertal breast development by repeated sampling via breast biopsies and serum collection. Our specific aims are: 1) to determine breast tissue responses to soy consumption during puberty; 2) to determine the effects of dietary soy on ovarian hormones during menarche and menstrual cycling; 3) to determine intratissue estrogens and the enzymes that regulate local estrogen production in the breast; and 4) to explore patterns of gene expression in mammary epithelium which may be modulated by soy consumption. The proposed work will provide a unique view of an otherwise inaccessible period of breast development in a primate model with high genetic and physiologic similarity to human beings.

描述（由申请人提供）：根据对女性的人口统计和观察研究，食用大豆与降低乳腺癌风险相关，并且在生命早期食用大豆时，其保护作用似乎更强。啮齿动物研究表明，对生命早期接触大豆异黄酮的动物具有深远的保护作用。我们在绝经后猴子模型中的数据清楚地表明，食用大豆对乳房具有抗增殖作用，而且我们还观察到，食用大豆会减少乳房的雌激素暴露。我们已经证明了猴子模型对绝经后乳腺癌风险的预测价值，我们相信该模型特别适用于青春期乳房发育的研究，而这在人类患者中很难进行研究。我们假设青春期食用大豆会减少乳房增殖，诱导乳房分化，并减少发育中乳房的激素暴露；这种效应可以解释为什么在生命早期接触大豆饮食的妇女和动物中观察到的乳腺癌风险较低。为了检验这一假设，我们建议将 40 只青春期前的雌性食蟹猴随机分组，接受高大豆饮食（模拟补充大豆的饮食）或不接受大豆饮食（模拟典型的北美饮食），并通过乳房活检和血清采集重复取样，纵向跟踪它们的月经初潮和青春期乳房发育过程。我们的具体目标是：1）确定青春期乳腺组织对大豆消费的反应； 2) 确定膳食大豆对初潮和月经周期期间卵巢激素的影响； 3) 确定组织内雌激素和调节乳房局部雌激素产生的酶； 4) 探索乳腺上皮中基因表达的模式，该模式可能受到大豆消耗的调节。拟议的工作将为在与人类具有高度遗传和生理相似性的灵长类动物模型中提供其他无法进入的乳房发育时期的独特视角。