In vitro effects of PCBs and OH-PCBs on the basal and dexamethasone-modified thyroid hormone metabolism in chicken liver

Abstract

To assess the in vitro effect of polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (OH - -PCBs) on the metabolism of thyroid hormones (THs) in chicken liver, explants of liver tissue were incubated in a medium supplemented with dexamethasone (DEX) (100 nM), PCB118 (dioxin-like PCB), PCB153 (non-dioxin-like PCB), 4-OH-PCB107 and 3-OH-PCB153 (0.5 × 10-8 M), and with DEX together with each of the PCBs and OH-PCBs to determine the triiodothyronine (T3) secretion, thyroxine (T4) to T3 conversion, mRNA expression and protein concentration of the iodothyronine deiodinases (DIO1, DIO2, DIO3), TH transporters (OATP1C1, MCT8, MCT10, LAT1) and TH receptors (THRA, THRB). The results obtained revealed that the tested PCBs and OH-PCBs interacted with and/or abolished the inhibitory effects of DEX on T3 secretion and T4 to T3 conversion. The tested dl- and ndl-PCBs and their hydroxylated metabolites affected the basal and DEX-modified mRNA expression and the protein concentration of all three deiodinases. The PCBs and OH-PCBs did not change the MCT8 gene expression; however, PCB118 and 4-OH-PCB107 reduced the MCT10 mRNA levels with a concomitant increase in the basal and DEX - -stimulated LAT1 mRNA expression. PCB153 and 3-OH-PCB153 did not influence the MCT10 expres- sion, but they elevated the basal and reduced DEX-stimulated LAT1 mRNA levels. Among the four tested PCBs, only 4-OH-PCB decreased the TRβ0 mRNA expression. In conclusion, to our knowledge, these results revealed for the first time that both dl-PCB and ndl-PCB and their OH-PCBs affect T3 secretion and T4 to T3 conversion, as well as the expression of iodothyronine deiodinases and TH transporters in chicken liver. These results indicate that not only the parental PCBs, but also their hydroxylated deriva - tives may influence iodothyronine metabolism in a chicken's liver, resulting in changes in T3 availability in the organism.