ABSTRACT
The goal of this study was to determine the effects of various compounds on the 17-beta-estradiol-induced dimerization of the human estrogen receptor alpha (hERalpha), a nuclear transcription factor. For this purpose, we used a modified yeast two-hybrid (YTH) bioassay designed to study protein-protein interactions, based on the electrochemical monitoring of hERalpha dimerization and detected as beta-D-galactosidase reporter gene activity in a synthetic substrate p-aminophenyl-beta-D-galactopyranoside (pAPG). Compared with 17-beta-estradiol activity, genistein, bisphenol-A (BPA), and naringenin induced dimerization to a lower extent by four, five and six magnitudes of orders of magnitude, respectively. In the presence of physiological concentrations of 17-beta-estradiol, both tamoxifen and the analgesic drug acetaminophen inhibited hER dimerization in an antiestrogenic manner.
