Molecular mechanism of endocrine disruption

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Exposure of wildlife and humans to environmental contaminants that behave as hormones has caused widespread alarm. Reproductive damages reported to date include reduced fertility, reduced hatchability, reduced viability of offspring, impaired hormone activity and altered sexual behavior. Chlorinated hydrocarbons, such as DDE and methoxychlor, and non ionic surfactants, such as nonylphenol, are among the chemicals of concern and these are present in sufficiently high concentrations to activate the estrogen cascade pathway, turning on the expression of genes controlled by estrogen at inappropriate times. In addition, another key modulator mechanism of action of environmental estrogens may be through non-estrogen receptor pathways, in particular estrogen-mediated altered regulation of xenobiotic transformation pathways. These include steroid oxidation pathways and phase II conjugation pathways. These include steroid oxidation pathways and phase II conjugation pathways. We have centered our studies on understanding the mechanisms involved in endocrine disruption of largemouth bass found in the highly polluted, superfund site at Lake Apopka and the much farms in the area of central Florida. We propose to study these species in laboratory in vivo and in vitro experiments to define the mechanisms involved. We also plan to develop an endocrine toxicology based gene expression array (DNA chip) specific for fish that can be used to detect exposure to endocrine disrupting compounds in the environment. Our specific aims include 1: Evaluation of mechanism for estrogen receptor based molecular change; 2: Characterization of the estrogen receptors alpha and beta in their model of action; 3. Determination of the effects of natural and synthetic estrogens on xenobiotic biotransformation; and 4: Development of an endocrine toxicology based gene expression array (DNA chip) to evaluate endocrine disruption. In the final phases of this project we will use the DNA chip to evaluate the gene induction status of fish from Lake Apopka and much farm regions.