Differential Interaction of the Methoxychlor Metabolite 2,2-Bis-(p-Hydroxyphenyl)-1,1,1-Trichloroethane with Estrogen Receptors α and β1

Concern that some chemicals in our environment may affect human health by disrupting normal endocrine function has prompted research on interactions of environmental contaminants with steroid hormone receptors. We compared the activity of 2,2-bis-(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE), an estrogenic metabolite of the organochlorine pesticide methoxychlor, at estrogen receptor α (ERα) and estrogen receptor β (ERβ). Human hepatoma cells (HepG2) were transiently transfected with either human or rat ERα or ERβ plus an estrogen-responsive, complement 3-luciferase construct containing a complement 3 gene promoter sequence linked to a luciferase reporter gene. After transfection, cells were treated with various concentrations of HPTE in the presence (for detecting antagonism) or absence (for detecting agonism) of 17β-estradiol. HPTE was a potent ERα agonist in HepG2 cells, with EC50 values of approximately 5 × 10−8 and 10−8 m for human and rat ERα, respectively. In contrast, HPTE had minimal agonist acti...