Evaluation of ligand selectivity using reporter cell lines stably expressing estrogen receptor alpha or beta

    loading  Checking for direct PDF access through Ovid


Estrogens control transcriptional responses through binding to two different nuclear receptors, estrogen receptor α (ERα) and β (ERβ). Since these two ER subtypes are thought to mediate different biological effects, there is intense interest in designing subtype-selective ER ligands. In this study, we evaluated the ERα and ERβ selectivity of 19 known estrogens and antiestrogens using reporter cell lines previously developed in our laboratory. The HELN-ERα and HELN-ERβ cells stably express full-length ERα and ERβ, respectively, and are derived from HELN cells (HeLa cells stably transfected with an ERE-driven luciferase plasmid). We report that 16α-LE2, PPT and 3β,5α-GSD have a high ERα-selective agonist potency while 8β-VE2, DPN, genistein and biochanin A show ERβ selectivity with 8β-VE2 being the most potent and selective ERβ agonist. We also tested ER antagonists and we showed that raloxifene and RU486 are ERα and ERβ-selective antiestrogens, respectively. In all cases, selectivity is due to differences in binding affinities as indicated by whole-cell ligand-binding assays. Very interestingly, we demonstrate that a combination of genistein and raloxifene produces a full-ERβ specific response. Together these results demonstrate the usefulness of our stably transfected cell lines to characterize ER ligands and indicate that treatments combining agonist/antagonist ligands produce full-ERβ selectivity.

    loading  Loading Related Articles