Species-Specific Endocrine Disruption: PCB- and PAH-Induced Estrogenic EffectsEPA Grant Number: R826301
Title: Species-Specific Endocrine Disruption: PCB- and PAH-Induced Estrogenic Effects
Investigators: Zacharewski, Timothy
Institution: Michigan State University
EPA Project Officer: Klieforth, Barbara I
Project Period: January 1, 1998 through December 31, 2000
Project Amount: $282,998
RFA: Endocrine Disruptors (1997) RFA Text | Recipients Lists
Research Category: Economics and Decision Sciences , Endocrine Disruptors , Health , Safer Chemicals
Accumulating evidence suggests that chemicals and complex mixtures are capable of eliciting endocrine disrupting activities that adversely affect human and wildlife health, and jeopardize environmental quality. Several studies have shown numerous species are experiencing compromised reproductive fitness and there has also been significant increases in the incidence of hormone-dependent cancers. It has been proposed that some of these effects may be due to exposure to chemicals and/or complex mixtures that possess estrogen receptor-mediated activities. These substances are commonly referred to as environmental estrogens.
Estrogens and the estrogen receptor (ER) play major roles in a number of physiological processes such as the regulation of developmental processes, homeostasis and fertility as well as in pathological conditions such as hormone-dependent diseases. Although the function and activities of estrogen and the ER are conserved between species, the amino acid sequence of the ligand binding domains of the ERs are less conserved. This suggests that species may exhibit different responses and sensitivities to non-traditional estrogenic ligands and that one species may not be an appropriate surrogate to identify and to assess the risks environmental estrogens pose to human and wildlife health. The intent of this proposal is to examine the estrogenic activities of polychlorinated biphenyls (PCBs) and polyaromatic hydrocarbons (PAHs) and to examine their effects in a number of species including rodents, birds, fish and amphibians.
Rodent, avian, aquatic and amphibian species exhibit different sensitivities to environmental estrogens due to different ligand preferences and binding affinities to the estrogen receptor.
An integrative approach will be used that involves a battery of in vitro and in vivo assays. Species specific differences in ligand preference and binding affinities initially identified using in vitro assays (i.e. receptor binding, gene expression) will subsequently be verified in vivo by monitoring gene expression (e.g. vitellogenin).