Cytosolic SULTs and Environmental Xenoestrogen Metabolism: A Zebrafish Model

Rhodora V.Snow，首席研究员，项目标题：胞浆磺基转移酶和环境异种雌激素代谢：斑马鱼模型环境异种雌激素包括能够模拟内源性雌激素的各种工业和农业化学品。近年来，它们被认为是导致野生动物发育和生殖异常的内分泌干扰物。在脊椎动物中，硫酸盐化是许多内源或外源化合物进行生物转化以满足各种生化/生理需求的一种机制。这些化合物在胞液磺酸转移酶(Sults)的催化下进行硫酸盐化，既可以调节甲状腺/类固醇激素和儿茶酚胺激素/神经递质的水平和活性，也可以解毒饮食和环境中的外来物质，包括外源雌激素。然而，考虑到胞质硫化物在内分泌系统的动态平衡和关键内源性化合物调节中的关键作用，过量的可硫化环境异种雌激素扰乱胞液硫化物的正常功能可能会导致内分泌紊乱。作为一种水生脊椎动物，斑马鱼是研究环境污染的外来雌激素不良影响的一个特别有用的模型。该项目的具体目标是：1.建立完整的斑马鱼胞质硫磺图谱，并用环境异种雌激素测定其酶活性。阐明硫酸盐化在调节外源雌激素类雌激素活性中的作用，研究外源雌激素的代谢命运及其对斑马鱼胚胎发育和繁殖潜力的影响。这些研究有望对胞质硫磺参与斑马鱼体内外源雌激素的调节和/或不利作用提供基本的见解。

Rhodora V. Snow, Principal InvestigatorTitle of Project: Cytosolic Sulfotransferases and Environmental Xenoestogen Metabolism: A Zebrafish ModelEnvironmental xenoestrogens comprise a diverse group of industrial and agricultural chemicals that are capable of mimicking endogenous estrogens. They have in recent years been implicated as endocrine disruptors that are responsible for the developmental and reproductive abnormalities in wildlife. In vertebrate animals, sulfation is employed as a mechanism by which many endogenous or exogenous compounds undergo biotransformation to fulfill various biochemical/physiological needs. Sulfation of these compounds, as catalyzed by the cytosolic sulfotransferases (SULTs), may serve to both regulate the levels and activities of thyroid/steroid hormones and catecholamine hormones/neurotransmitters, as well as detoxify dietary and environmental xenobiotics, including xenoestrogens. Considering the critical roles of cytosolic SULTs in the homeostasis and modulation of key endogenous compounds of the endocrine system, however, perturbation of the normal functioning of the cytosolic SULTs by excess sulfatable environmental xenoestrogens may lead to endocrinologic disorders. As an aquatic vertebrate, the zebrafish serves as a particularly useful model for studying the adverse effects of polluting environmental xenoestrogens. The specific aims of the project are:1. To establish a complete repertoire of zebrafish cytosolic SULTs and determine their enzymatic activities with environmental xenoestrogens.2. To elucidate the role of sulfation in modulating the estrogenic activities of xenoestrogens and investigate the metabolic fates of xenoestrogens and their effects on embryonic development and reproductive potential of zebrafish. These studies are anticipated to yield fundamental insights into the involvement of the cytosolic SULTs in the modulation and/or adverse functioning of xenoestrogens in zebrafish.