Interaction of PAH-related compounds with the α and β isoforms of the estrogen receptor

The ability of several 4- and 5-ring polycyclic aromatic hydrocarbons (PAHs), heterocyclic PAHs, and their monohydroxy derivatives to interact with the estrogen receptor (ER) alpha and beta isoforms was examined. Only compounds possessing a hydroxyl group were able to compete with ³H-labeled 17β-estradiol (E2) for binding to either a glutathione-S-transferase and human ERα D, E, and F domain fusion protein (GST-hERαdef) or to the full-length human ERβ. Competitive binding was comparable for both isoforms, with IC₅₀ values ranging from 20 to 300 nM (E2 IC₅₀ approximately 3 nM). However, several compounds were able to induce reporter gene expression preferentially through mERβ, using MCF-7 cells transiently transfected with either a Gal4-human ERαdef or Gal4-mouse ERβdef construct, as well as a Gal4-regulated reporter. These data extend the number and type of PAH-related compounds capable of interacting with ERα and ERβ, and provides additional evidence that even though some compounds may possess a similar affinity for both ER isoforms, the capacity for transcriptional activation can still be isoform-specific.