Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 275 (46), 35986-93

Differential Effects of Xenoestrogens on Coactivator Recruitment by Estrogen Receptor (ER) Alpha and ERbeta

Affiliations

Differential Effects of Xenoestrogens on Coactivator Recruitment by Estrogen Receptor (ER) Alpha and ERbeta

E J Routledge et al. J Biol Chem.

Abstract

It has been proposed that tissue-specific estrogenic and/or antiestrogenic actions of certain xenoestrogens may be associated with alterations in the tertiary structure of estrogen receptor (ER) alpha and/or ERbeta following ligand binding; changes which are sensed by cellular factors (coactivators) required for normal gene expression. However, it is still unclear whether xenoestrogens affect the normal behavior of ERalpha and/or ERbeta subsequent to receptor binding. In view of the wide range of structural forms now recognized to mimic the actions of the natural estrogens, we have assessed the ability of ERalpha and ERbeta to recruit TIF2 and SRC-1a in the presence of 17beta-estradiol, genistein, diethylstilbestrol, 4-tert-octylphenol, 2',3',4', 5'-tetrachlorobiphenyl-ol, and bisphenol A. We show that ligand-dependent differences exist in the ability of ERalpha and ERbeta to bind coactivator proteins in vitro, despite the similarity in binding affinity of the various ligands for both ER subtypes. The enhanced ability of ERbeta (over ERalpha) to recruit coactivators in the presence of xenoestrogens was consistent with a greater ability of ERbeta to potentiate reporter gene activity in transiently transfected HeLa cells expressing SRC-1e and TIF2. We conclude that ligand-dependent differences in the ability of ERalpha and ERbeta to recruit coactivator proteins may contribute to the complex tissue-dependent agonistic/antagonistic responses observed with certain xenoestrogens.

Similar articles

See all similar articles

Cited by 82 PubMed Central articles

See all "Cited by" articles

Publication types

MeSH terms

Substances

LinkOut - more resources

Feedback