Differential activation by xenoestrogens of ERα and ERβ when linked to different response elements

Abstract

The discovery of a second estrogen receptor (ERβ) has significant implications for our understanding of the molecular basis for the diverse actions of estrogen. Here we report the differential activation by natural and xenobiotic estrogens of ERa and ERβ when linked to different response elements. Receptor mediated activation of reporter constructs containing either the estrogen response element (ERE) from the vitellogenin (Vit) gene or from the luteinizing hormone β (LH) gene were examined in transiently transfected Cos-1 cells. ERβ preferentially activated the consensus Vit ERE whereas ERa showed greater activation at the divergent LH ERE. This differential activation was observed for a number of ligands including estradiol, estrone, bisphenol A, octylphenol and diethystilbestrol. These findings show that the nature of the ERE, as well as the ratio of ER subtypes in a particular cell/tissue, will influence whether particular estrogen responsive genes are activated in the presence of natural or xenobiotic estrogens.