Cytosolic SULTs and Environmental Xenoestrogen Metabolism: A Zebrafish Model

Rhodora V. Snow，首席研究员 项目名称：胞质磺基转移酶和环境异雌激素代谢：斑马鱼模型环境异雌激素由多种能够模仿内源雌激素的工业和农业化学品组成。 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，硫酸化被用作许多内源性或外源性化合物进行生物转化以满足各种生化/生理需求的机制。在胞质磺基转移酶 (SULT) 的催化下，这些化合物的硫酸化可能有助于调节甲状腺/类固醇激素和儿茶酚胺激素/神经递质的水平和活性，以及​​解毒饮食和环境异生物质，包括异雌激素。然而，考虑到胞质 SULT 在内分泌系统关键内源性化合物的稳态和调节中的关键作用，过量硫酸化环境异雌激素对胞质 SULT 正常功能的干扰可能导致内分泌紊乱。 作为一种水生脊椎动物，斑马鱼是研究污染环境异种雌激素的不利影响的特别有用的模型。 该项目的具体目标是： 1．建立斑马鱼胞质SULTs完整谱系，并用环境异雌激素测定其酶活性。 2．阐明硫酸化在调节异种雌激素的雌激素活性中的作用，并研究异种雌激素的代谢命运及其对斑马鱼胚胎发育和生殖潜力的影响。这些研究有望对胞质 SULT 在斑马鱼异种雌激素的调节和/或不利功能中的参与产生基本的见解。

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.