Use of a Transgenic Yeast Line to Determine the Estrogenicity and Potential Health Risk of Bisphenol Plasticizers Binding to the Estrogen Receptor

Abstract

Two main types of estrogen receptors, Estrogen Receptor α (ERα) and β (ERβ) are differentially expressed in tissues through the human body. Once activated through ligand binding, these nuclear transactivating receptors homodimerize and bind to Estrogen Response Elements (EREs) on the DNA, and either stimulate or repress the transcription of downstream genes. Depending on the type of receptor activated, the specific ligand bound, the intracellular conditions, and the co-factors bound a wide variety of effects can be observed including the expression of cell growth and replication proteins. Over-activation of ERs, in particular ERα, can lead to many uncontrolled cell proliferation increasing the risk of developing cancers. Bisphenols are hydrophobic compounds used in polymer synthesis and can leach into food and water from their plastic containers. Bisphenols can mimic ER ligands and can activate these receptors, potentially leading to an increase in the risk of developing developmental disorders and cancer. This study will look into the effects of this binding on ERα. To do so, we will be using a transgenic yeast line that expresses human ERα, and contains plasmids containing bacterial luciferase (lux) genes downstream of EREs. When the ERα is activated by an agonist more lux will be expressed which will luminesce and this luminescence can be detected to gauge how much ER activity is taking place after ligand binding. By comparing the dose dependent activity curves for bisphenols with the endogenous estrogen we can estimate the estrogenicity of bisphenol compounds. We can then test the estrogenic activity of bisphenols present in plastics used as containers for liquids intended for human consumption.