Project 1
Endocrine Disruptors : Mechanistic Studies
There is widespread concern over potential adverse human health effects associated with exposures to endocrine-active industrial chemicals. Based on results of preliminary studies with bisphenol A, we hypothesize that different structural classes of xenoestrogens and naturally-occurring estrogenic compounds exhibit "unique" estrogenic activities and unique biologies that cannot be determined using traditional bioassays.
Major Objectives
Six different structural classes of estrogenic compounds are being investigated in the HepG2 cell assay to determine their specific mechanism-based ER action.
Ligand structure-dependent differences are also being studied in a variety of cancer cell lines to investigate their receptor ag-onist and antagonist activities.
Ligand-dependent differences in activation of ERa vs. ERb are also being investigated using newly developed assays.
In Vivo models used to study xenoestrogen activation of ERa and ERb are being utilized to improve mechanism-based hazard/ risk-specific induction of gene expression.
Highlights
The pattern of in vitro ERa activation by synthetic and phytochemical-based estrogenic compounds suggests that these chemicals may exhibit "unique" in vivo biologies.
HPTE and some structurally-related methoxychlor metabolites exhibit ERa agonist and ERb antagonist responses.
