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Cytosolic SULTs and Environmental Xenoestrogen Metabolism: A Zebrafish Model

$175,000FY2006BIONSF

Jarvis Christian College, Hawkins TX

Investigators

Abstract

Rhodora V. Snow, Principal Investigator Title of Project: Cytosolic Sulfotransferases and Environmental Xenoestogen Metabolism: A Zebrafish Model Environmental 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.

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