Hydroxylated polybrominated diphenyl ethers exhibit different activities on thyroid hormone receptors depending on their degree of bromination

摘要: Polybrominated diphenyl ethers (PBDEs) have been shown to disrupt thyroid hormone (TH) functions in experimental animals, and one of the proposed disruption mechanisms is direct binding hydroxylated PBDE (OH-PBDE) TH receptors (TRs). However, previous data on receptor activity OH-PBDEs were very limited sometimes inconsistent. In present paper, we examined potency ten with different degrees bromination TR using a fluorescence competitive assay. The results showed that bound correlated their level. We further effect coactivator assay GH3 cell proliferation Different activities observed depending degree bromination. Four low-brominated (2'-OH-BDE-28, 3'-OH-BDE-28, 5-OH-BDE-47, 6-OH-BDE-47) found be agonists, which recruited peptide enhanced proliferation. three high-brominated (3-OH-BDE-100, 3'-OH-BDE-154, 4-OH-BDE-188) tested antagonists. Molecular docking was employed simulate interactions identify structural determinants for activity. According results, OH-PBDEs, are weak binders but bind at inner side its pocket, whereas compounds, potent antagonists, reside outer region. These indicate (agonistic or antagonistic), possibly due geometries receptor.