Thyroid hormone receptor-mediated transcription is suppressed by low dose Phthalate

Summary: Phthalates are synthetic chemicals used mainly as solvents, additives and plasticizers in polyvinylchloride (PVC) products to increase their flexibility. Phthalate plasticizers are not chemically bound to PVC, so they easily leach into the environment. There is currently heightened concern about potential health risk, especially endocrine disrupting effects associated with the use of these chemicals. We therefore investigated the effects of phthalate on thyroid hormone receptor (TR)-mediated transcription using transient transfection studies and found that low dose phthalate (10^-7) M suppressed thyroid hormone (TH)-induced TR-mediated transcription by 30%. We further examined the effect of phthalate on TR-thyroid hormone response element (TRE) binding, and found no dissociation of TR from TRE. Phthalate did not also dissociate coactivator (steroid receptor coactivator-1) from TR neither did it recruit corepressor (nuclear corepressor; NCoR) to TR in the presence of TH. Our results indicate that low phthalate can disrupt TR-mediated gene expression and interfere with TH balance in TH-sensitive organs including the developing brain.