Carbaryl, 1-naphthol and 2-naphthol inhibit the beta-1 thyroid hormone receptor-mediated transcription in vitro.
Effects of pesticides on the function of thyroid have attracted lots of attention because thyroid hormones (THs) play a major role in mammalian brain development. In order to screen for compounds that acted on the thyroid hormone receptor (TR) signaling pathway, we transiently transfected the vector pGal4-L-TRbeta1 (Gal4 DBD fused to hTRbeta1 LBD) and Gal4-responsive luciferase reporter pUAS-tk-Luc into HepG2 cell, developing a reporter gene assay which showed good response to triiodothyronine (T3) and thyroxine (T4) with the median effective concentration (EC(50)) of 0.46 and 25.53 nM, respectively. Bisphenol A exhibited weak anti-thyroid hormone activity with median inhibitory concentration (IC(50)) value of 6.45 x 10(-5)M. The assay showed acceptable repeatability to T3 with intra coefficient of variability (CV) of 5.9% and inter CV of 11.7%. Carbaryl, 1-naphthol (1-NAP) and 2-naphthol (2-NAP) were tested for their agonist and antagonist activities. As a result, we found that all the three related chemicals possessed TR antagonist activity and none of them showed the agonist activity. These results further indicated that TR might be the targets of industrial chemicals. And this assay provided a useful tool for investigating the effects of environment chemicals on thyoid function.
Sun
Hong
H
Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, China.
Shen
Ou-Xi
OX
Xu
Xiao-Lin
XL
Song
Lin
L
Wang
Xin-Ru
XR
D001559:Benzhydryl Compounds; D012721:Carbaryl / Q000494:pharmacology*; D002460:Cell Line; D017930:Genes, Reporter / Q000187:drug effects; D006801:Humans; D007306:Insecticides / Q000494:pharmacology*; D008024:Ligands; D008156:Luciferases / Q000235:genetics; D009284:Naphthols / Q000494:pharmacology*; D010636:Phenols / Q000494:pharmacology; D010957:Plasmids / Q000235:genetics; D037042:Thyroid Hormone Receptors beta / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects*; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D012721:Carbaryl; D007306:Insecticides; D008024:Ligands; D008156:Luciferases; D009284:Naphthols; D010636:Phenols; D037042:Thyroid Hormone Receptors beta; C029350:1-naphthol; C006780:bisphenol A; D000098826:Bisphenol A Compounds; C028405:2-naphthol