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 TRβ1 and significantly elevated endogenous growth hormone (GH) expression in GH3 cells in a manner similar to that of T3 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 TRβ1 to physically interact with the TRE in the GH promoter, or with SRC1 or NCoR. These effects were directly parallel to effects of T3, indicating that 4-OH-CB106 exerts a direct agonistic effect on the TRβ1.