Botanical Estrogen Actions in Bone, Uterus, Mammary,and Breast/William Helferich

项目总结(见说明)： 作为用于激素替代疗法的标准雌激素药物的替代品，许多 年长的女性正在使用植物雌激素来治疗更年期症状，认为这些饮食 补充剂本质上是安全的，因为它们是天然的。此外，由于治疗方法的改进，许多人 乳腺癌幸存者在乳腺癌发生后可以活很多年，其中相当一部分人 这些妇女正在使用这些植物药物，希望它们能帮助控制她们的疾病。这个 本项目的总体目标是评估植物雌激素对重要雌激素靶点的活性。 对组织和乳腺癌转移的影响。在目标1中，我们将研究植物雌激素的作用。 (来自大豆、野山药、甘草和东瓜)对三个重要的靶组织，骨，子宫和 在小鼠和大鼠的乳腺中，将它们的作用与已知雌激素-雌激素受体的作用进行比较 亚型选择性配体和选择性雌激素受体调节剂。在目标2中，我们将评估这些影响 植物雌激素对乳腺癌骨内生长和进展及随后转移的影响 肺和其他内脏部位，在临床前动物模型中使用活体生物发光成像， 病理和组织学检查，以及与以下相关的基因表达谱分析 转移活跃性。这些发现可能与人类健康有关，因为转移到骨和肺 是女性乳腺癌扩散的主要途径，极大地增加了发病率和死亡率。 植物、提取物、组分和纯分离物将从核心A获得，剂量由核心确定 B.本项目的工作将受益于植物雌激素的机理研究结果 在项目1中，将与从项目3获得的老年动物骨骼健康研究相结合。 总而言之，这些研究的结果将有助于确定植物雌激素对 临床前啮齿动物模型中雌激素靶向组织及对小鼠肿瘤进展和转移的影响 模特。这些发现对于理解使用的植物雌激素的作用和安全性将是重要的。 是女人干的。

PROJECT SUMMARY (See instructions): As alternatives to the standard estrogen pharmaceuticals used for hormone replacement therapy, many older women are using botanical estrogens to treat menopausal symptoms, believing that these dietary supplements are inherently safe because they are natural. Also, because of improved therapies, many breast cancer survivors are living for many years after their breast cancer arises, and a significant number of these women are using these botanicals in the hope that they will help in managing their disease. The overall goal ofthis project is to evaluate the activity of botanical estrogens on important estrogen target tissues and on breast cancer metastasis. In Aim 1, we will investigate the effects of botanical estrogens (from soy, wild yam, licorice root, and dong quai) on three important target tissues, bone, uterus, and mammary gland, in mice and rats, comparing their effects with that of known estrogens, estrogen receptor subtype-selective ligands, and selective estrogen receptor modulators. In Aim 2, we will evaluate the effects of botanical estrogens on the growth and progression of breast cancer in bone and subsequent metastasis to lung and other visceral sites, in a pre-clinical animal model using in vivo bioluminescence imaging, pathological and histological examination, and analysis of gene expression profiles that correlate with metastatic activity. These findings could be relevant to human health, because metastases to bone and lung are major routes of breast cancer expansion in women and contribute greatly to morbidity and mortality. Botanicals, extracts, fractions and pure isolates will be obtained from Core A, with doses determined by Core B. The work in this project will benefit from the results of the mechanistic studies on the botanical estrogens in Project 1 and will interface with the studies on bone health in older animals obtained from Project 3. Collectively, results from these studies will enable determination ofthe effects of botanical estrogens on estrogen target tissues in pre-clinical rodent models and on cancer progression and metastasis in a mouse model. These findings will be important in understanding the actions and safety of botanical estrogens used by women.