4-Hydroxy-PCB106 acts as a direct thyroid hormone receptor agonist in rat GH3 cells.
Polychlorinated biphenyls (PCBs) may interfere with thyroid hormone (TH) action by interacting directly with the TH receptor (TR). We found that the hydroxylated PCB metabolite, 4-OH-CB106, bound to the human TRbeta1 and significantly elevated endogenous growth hormone (GH) expression in GH3 cells in a manner similar to that of T(3) itself. This effect was also observed using a consensus TH response element (TRE) in a luciferase expression system, and was blocked by a single base-pair substitution in this TRE. In addition, we found that 4-OH-CB106 did not alter the ability of TRbeta1 to physically interact with the TRE in the GH promoter, or with SRC1 or NCoR. These effects were directly parallel to effects of T(3), indicating that 4-OH-CB106 exerts a direct agonistic effect on the TRbeta1.
You
Seo-Hee
SH
Program in Molecular & Cellular Biology, University of Massachusetts-Amherst, Amherst, MA 01003, USA.
Gauger
Kelly J
KJ
Bansal
Ruby
R
Zoeller
R Thomas
RT
D000818:Animals; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation / Q000379:methods; D004268:DNA-Binding Proteins / Q000187:drug effects; D017930:Genes, Reporter / Q000187:drug effects; D013006:Growth Hormone / Q000235:genetics / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000378:metabolism / Q000633:toxicity*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051381:Rats; D011988:Receptors, Thyroid Hormone / Q000819:agonists*; D020218:Response Elements / Q000187:drug effects; D037042:Thyroid Hormone Receptors beta / Q000819:agonists / Q000378:metabolism; D013963:Thyroid Hormones / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection
D004268:DNA-Binding Proteins; D011988:Receptors, Thyroid Hormone; D037042:Thyroid Hormone Receptors beta; D013963:Thyroid Hormones; D013006:Growth Hormone; D011078:Polychlorinated Biphenyls; D008156:Luciferases