CELLULAR MECHANISMS OF ENDOCRINE DISRUPTERS

描述：（改编自申请人的描述）许多化合物，如 杀虫剂，增塑剂和二恶英可被归类为环境 雌激素或内分泌干扰物。 妇女接触这些化学品的情况 环境、食物链和职业暴露， 影响妇女的健康，并通过出生缺陷的增加， 后人 该提案审查了一组化学品，以确定其潜在的 影响妇女的健康和未来后代的健康。 这些研究 将研究这些化合物在雌激素和 非雌激素途径，以及这些途径所使用的生物学机制 基因调控中的化合物。 假设每种化合物都影响 将测试雌激素途径。 将使用一种新的测定方法来确定 与雌激素受体结合。 组织培养中的基因调控研究 系统将用于确定这些化合物的能力， 作为激动剂或拮抗剂参与雌激素的已知机制 基因调控 将使用差异显示PCR来确定是否 化合物可以通过雌激素或 非雌激素途径。 最后，这些体外研究的结果将 在动物身上得到证实，使用最近创建的雌激素受体 “敲除”小鼠和正常同窝小鼠。

DESCRIPTION: (adapted from applicant's description) Many compounds such as insecticides, plasticizers, and dioxins can be classified as environmental estrogens or endocrine disrupters. Exposure of women to these chemicals in the environment, in the food chain, and through occupational exposures, may affect women's health and, through increases in birth defects, the health of future generations. This proposal examines a panel of chemicals to determine their potential to affect women's health and the health of future offspring. These studies will examine the regulatory potential of these compounds in estrogenic and non-estrogenic pathways, and the biological mechanisms used by these compounds in gene regulation. The hypothesis that each compound affects estrogenic pathways will be tested. A novel assay will be used to determine binding to estrogen receptor. Gene regulation studies in tissue culture systems will be used to determine the capacity of these compounds to participate as agonists or antagonists in known mechanisms of estrogenic gene regulation. Differential display PCR will be used to determine if compounds can alter endogenous gene expression by estrogenic or non-estrogenic pathways. Finally, results from these in vitro studies will be confirmed in animals, using the recently created estrogen receptor "knock-out" mouse and normal litter mates.