Understanding the interaction of estrogenic ligands with estrogen receptors: a survey of the functional and binding kinetic studies

Abstract

The investigation of estrogen actions and their interaction characteristics with estrogen receptors (ERs) to induce unique functional features inside cells have allowed us to understand better the regulation of many vital physiological and cellular processes in humans. The biological effects of estrogenic ligands or compounds are mediated via estrogen receptors that act as the ligand-activated transcription factors. Therefore, the study on ligand-ER interaction properties and mechanism of ligand-ER complexes binding to specific estrogen response elements located in the promoters of target genes are very critical to realize the complicated biological process regulated by the endogenous estrogens. Several reviews have provided comprehensive and updated information on the influence of estrogen receptors in health and disease. However, the mechanism of estrogen-ERs binding and affinity aspects at molecular level is relatively under-investigated. This review thus aims to shed light on the significance of the binding kinetics of ligand-ER interactions because the information provide great assistance to define how a ligand or a drug can communicate with physiology to produce a desired therapeutic response. In addition, the most frequently used methodologies for the binding kinetic study are highlighted over the last decade.

Keywords: Endocrine disruptors; estrogen receptors; estrogen–estrogen receptor interactions.