INFLUENCE OF BENZO(A)PYRENE ON OVARIAN FUNCTION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 注：表格和数字与整个研究总结文件一起上传。 背景 多环芳烃(PAH)家族包括100种不同的化合物，其中一种是苯并(A)芘(BaP)。这些化合物来自自然来源和涉及高温热解过程的合成来源，然而，来自合成来源的多环芳烃在环境中的数量分布更多。人体暴露的来源虽然不是一个详尽的清单，但包括：家庭取暖和用煤或木头做饭、香烟烟雾、汽车尾气排放、受污染的食品、焦炭、石墨电极和碳阳极制造行业。 BaP及其代谢物与E2的立体相似性赋予了这些分子雌激素和抗雌激素活性。BaP的雌激素效应主要表现在对人乳腺末梢导管细胞增殖的促进作用以及对E_2代谢的影响。相反，BaP和其他多环芳烃通过降低循环中的E2水平来显示其抗雌激素活性。循环中E_2的减少既可以通过BaP诱导的E_2合成和释放减少，也可以通过肝脏细胞色素P-450酶促进E_2代谢而发生。E_2减少的最终结果是E_2受体合成减少，E_2介导的生物学功能减少，特别是在卵巢。 由于多环芳烃在环境中的广泛可获得性和相当大的人类暴露概率，这种化合物对哺乳动物卵巢功能的潜在不利影响值得研究。 具体目标 1)测定苯并(A)芘在雌性大鼠体内的生物利用度和毒代动力学。 2)研究BaP对大鼠发情周期中性腺类固醇及调节性腺激素的垂体激素水平的影响。 3)探讨BaP对卵巢外分泌功能和黄体维持的影响。 4)探讨BaP对受精和着床前发育的影响。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. NOTE: Tables and Figures were uploaded with the Overall Research Summary file. BACKGROUND The polycyclic aromatic hydrocarbon (PAH) family includes 100 different compounds one of them being benzo(a)pyrene (BaP). These compounds are formed from natural and synthetic sources that involve high-temperature pyrolytic processes, however, PAHs originating from synthetic sources are quantitatively more distributed in the environment. Sources of human exposures, albeit not an exhaustive list, include: home heating and cooking with coal or wood, cigarette smoke, automobile exhaust emissions, contaminated foods, manufacturing industries for coke, graphite-electrode and carbon-anode. The steric resemblance of BaP and their metabolites to E2 confers estrogenic and antiestrogenic activity to these molecules. Estrogenic effect of BaP is exemplified in its ability to promote the proliferation as well as the alteration of E2 metabolism of human mammary terminal duct cell cultures. On the contrary, BaP and other PAHs exhibit their antiestrogenic activity by decreasing circulating levels of E2. The reduction in circulating E2 could occur either by BaP-induced decreases in the synthesis and release of E2 or via the enhancement of E2 metabolism by liver cytochrome P-450 enzyme. The ultimate result of the reduction in E2 is the reduction of E2 receptor synthesis and E2 mediated biological function particularly in the ovaries. Because of the widespread availability of PAH in the environment and the considerable probability of human exposure, the potential adverse effects of this compound the functioning of the mammalian ovary merit investigation. SPECIFIC AIMS 1) To determine the bioavailability and toxicokinetics of benzo(a)pyrene in female rats. 2) To determine the effect of BaP treatment on plasma concentrations of gonadal steroids and the pituitary hormones that regulate these steroids during the rat estrous cycle. 3) To determine the effect of BaP on ovarian exocrine function and luteal maintenance. 4) To determine the effect of BaP on fertilization and pre-implantation development.