INTERACTION OF DIOXINS AND ESTROGENS TO BLOCK OVULATION

2,3,7,8-四氯二苯并-对二恶英（TCDD）是二恶英中毒性最大的一种，也是EPA调查过的最有效的环境毒素之一。我们的实验室最近显示了TCDD对排卵的剂量依赖性抑制。虽然这种排卵阻断的确切机制尚不清楚，但其效果似乎主要是直接作用于卵巢的结果，并且由于先前暴露于雌激素（另一类环境内分泌干扰物）而被夸大。这种排卵中断很可能是环境雌激素和TCDD降低生育能力的一种机制。我们目前的工作旨在了解TCDD和雌激素如何在排卵阻断中相互作用。使用一个垂体切除的rt模型，本提案中概述的实验旨在1)表征雌激素夸大TCDD对排卵抑制的能力2)确定卵巢内雌激素和TCDD的靶组织3)评估雌激素和TCDD与芳烃受体基因的相互作用。该项目的长期目标是确定TCDD和雌激素相互作用以防止排卵的机制，并将这些知识应用于环境雌激素和二恶英的研究。

DESCRIPTION 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) is the most toxic of the dioxins and is one of the most potent environmental toxins ever investigated by the EPA. Our laboratory has recently shown a dose-dependent inhibition of ovulation by TCDD. Although the exact mechanisms of this ovulation blockade is unknown, the effect seems primarily to be the result of direct action(s) on the ovary and is exaggerated by previous exposure to estrogens (another class of environmental endocrine disrupter). Such interruption of ovulation might well be one mechanism by which environmental estrogens and TCDD diminish fertility. Our current work is intended to learn how TCDD and estrogens interact in the blockade of ovulation Using a hypophysectomized rt model, the experiments outlined in this proposal are intended to 1) characterize the ability of estrogens to exaggerate the suppression of ovulation by TCDD 2) determine the target tissues of estrogen and TCDD within the ovary 3) assess the interaction of estrogen and TCDD with the aryl hydrocarbon receptor gene. The long term goal of this project is to determine the mechanism by which TCDD and estrogens interact to prevent ovulation and apply this knowledge to the study of environmental estrogens and dioxins.