Asnake Solomon, Pradhan Ajay, Kharlyngdoh Joubert Banjop, Modig Carina, Olsson Per-Erik
Biology, The Life Science Center, School of Science and Technology, Örebro University, Örebro, Sweden..
Toxicol In Vitro. 2015 Dec;29(8):1993-2000. doi: 10.1016/j.tiv.2015.08.009. Epub 2015 Aug 28.
Increased exposure of birds to endocrine disrupting compounds has resulted in developmental and reproductive dysfunctions. We have recently identified the flame retardants, allyl-2,4,6-tribromophenyl ether (TBP-AE), 2-3-dibromopropyl-2,4,6-tribromophenyl ether (TBP-DBPE) and the TBP-DBPE metabolite 2-bromoallyl-2,4,6-tribromophenyl ether (TBP-BAE) as antagonists to both the human androgen receptor (AR) and the zebrafish AR. In the present study, we aimed at determining whether these compounds also interact with the chicken AR. In silico modeling studies showed that TBP-AE, TBP-BAE and TBP-DBPE were able to dock into to the chicken AR ligand-binding pocket. In vitro transfection assays revealed that all three brominated compounds acted as chicken AR antagonists, inhibiting testosterone induced AR activation. In addition, qRT-PCR studies confirmed that they act as AR antagonists and demonstrated that they also alter gene expression patterns of apoptotic, anti-apoptotic, drug metabolizing and amino acid transporter genes. These studies, using chicken LMH cells, suggest that TBP-AE, TBP-BAE and TBP-DBPE are potential endocrine disrupters in chicken.
鸟类接触内分泌干扰化合物的增加已导致发育和生殖功能障碍。我们最近已确定阻燃剂烯丙基-2,4,6-三溴苯基醚（TBP-AE）、2-3-二溴丙基-2,4,6-三溴苯基醚（TBP-DBPE）以及TBP-DBPE代谢物2-溴烯丙基-2,4,6-三溴苯基醚（TBP-BAE）是人类雄激素受体（AR）和斑马鱼AR的拮抗剂。在本研究中，我们旨在确定这些化合物是否也与鸡AR相互作用。计算机模拟研究表明，TBP-AE、TBP-BAE和TBP-DBPE能够对接至鸡AR配体结合口袋。体外转染试验显示，所有三种溴化化合物均作为鸡AR拮抗剂，抑制睾酮诱导的AR激活。此外，qRT-PCR研究证实它们作为AR拮抗剂起作用，并表明它们还改变凋亡、抗凋亡、药物代谢和氨基酸转运基因的基因表达模式。这些使用鸡LMH细胞的研究表明，TBP-AE、TBP-BAE和TBP-DBPE是鸡体内潜在的内分泌干扰物。
