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）：饮食中的大豆消费与女性人口统计学和观察性研究的乳腺癌风险降低有关，当大豆寿命早期消费时，保护效果似乎会更强。啮齿动物的研究表明，对大豆异黄酮的生命早期暴露的动物具有深远的保护作用。我们的绝经后猴子模型中的数据清楚地表明了大豆消耗对乳房的抗增殖作用，我们还观察到大豆消耗可减少乳腺的雌激素暴露。我们已经证明了绝经后环境中猴子模型对乳腺癌风险的预测价值，并且我们认为该模型特别适用于青春期乳房发育研究，这在人类患者中很难研究。我们假设青春期期间的饮食大豆消耗可以减少乳房增殖，诱导乳房分化并减少激素暴露于发育中的乳房。这种效果将解释观察到的乳腺癌风险较低的妇女和动物，暴露于大豆饮食的早期。为了检验这一假设，我们建议将40个前女性cynomolgus猴子随机化，以接受高肥大的饮食（对大豆补充的饮食进行建模）或饮食中的大豆（建模典型的北美饮食），并通过重复的乳房和狂热的乳液来进行逐渐发展，并通过重复的乳液来促进练习。我们的具体目的是：1）确定青春期对大豆消耗的乳腺组织反应； 2）确定饮食大豆对初潮和月经循环过程中卵巢激素的影响； 3）确定调节乳房中局部雌激素的雌激素的雌激素内雌激素和酶； 4）探索乳腺上皮中基因表达的模式，这可以通过大豆消耗来调节。拟议的工作将在具有与人类的遗传和生理相似性的灵长类动物模型中提供原本无法访问的乳房发育时期的独特视图。