Characterisation of the molecular responses to xenoestrogens using gene expression profiling

Abstract

The two estrogen receptors (ERs), ERαand ERβ, are molecular targets of the xenoestrogen class of endocrine disruptors. These receptors are ligand-activated transcription factors regulated by naturally occurring estrogens. Activation of mammalian ERs by xenoestrogens has been associated with both adverse and beneficial effects. A more informed appraisal of the likely risks and benefits of xenoestrogens requires an understanding of their biological effects at the molecular level. Receptor binding and reporter-based transient transfection assays indicate that some compounds, including the phytoestrogens genistein and coumestrol, activate ERβpreferentially, suggesting that this receptor subtype may play a predominant role in mediating the effects of these compounds. We review recent advances in our understanding of the responses of mammalian cells to estrogenic compounds and describe an approach to decipher these effects at the molecular level.