Winter 2005, ESEP-21 Seminar series:

February 18, 4:00 to 5:00 pm, Room 1200 EECS (North Campus)

Endocrine Disruptor Mechanisms: Beyond Receptor Binding

John P. Giesy
Distinguished Professor
Dept. Zoology and National Food Safety and Toxicology Center
Michigan State University

Abstract

It has long been known that synthetic organic compounds can cause adverse effects to humans and wildlife due to chronic exposures. These effects can be through diverse mechanisms of action. Recently, national legislation in North America and Europe has focused attention on the potential for some compounds to modulate the endocrine system. Initially, this concern focused on compounds that could mimic hormone, especially those that were estrogen agonists. For this reason, currently screening of compounds for their potential to modulate the endocrine system has focused on the development of in vitro assays based on the measurement or the prediction of the potential for compounds to bind to estrogen or androgen receptors. While this provides useful information, it should not be used as the sole screening endpoint to determine if compounds have endocrine modulating potential. Here I present the results of studies on the mechanisms of action of two environmentally relevant residues, atrazine and 2,3,7,8-TCDD. These results demonstrate that these compounds can modulate the endocrine system either through altered steroidogenesis or signal transduction pathways in a manner that would not be discovered by screening of receptor binding. In addition, I present a proposed assay to rapidly screen for steroidogenesis.


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