In Vitro Assay Shows That PCB Metabolites Completely Saturate Thyroid Hormone Transport Capacity in Blood of Wild Polar Bears (Ursus maritimus)

Abstract

Persistent chemicals accumulate in the arctic environment due to their chemical reactivity and physicochemical properties and polychlorinated biphenyls (PCBs) are the most concentrated pollutant class in polar bears (Ursus maritimus). Metabolism of PCB and polybrominated biphenyl ether (PBDE) flame-retardants alter their toxicological properties and these metabolites are known to interfere with the binding of thyroid hormone (TH) to transthyretin (TTR) in rodents and humans. In polar bear plasma samples no binding of [125I]-T(4) to TTR was observed after incubation and PAGE separation. Incubation of the plasma samples with [14C]-4-OH-CB107, a compound with a higher binding affinity to TTR than the endogenous ligand T(4) resulted in competitive binding as proven by the appearance of a radio labeled TTR peak in the gel. Plasma incubation with T(4) up to 1 mM, a concentration that is not physiologically relevant anymore did not result in any visible competition. These results give evidence that the binding sites on TTR for T(4) in wild living polar bears are completely saturated. Such saturation of binding sites can explain observed lowered levels of THs and could lead to contaminant transport into the developing fetus.

Anthropogenic flank attack on polar bears: interacting consequences of climate warming and pollutant exposure

“…In polar bears, the thyroid hormone system is sensitive to the effects of several POPs (Skaare et al, 2001;Braathen et al, 2004;Gutleb et al, 2010;Knott et al, 2011;Villanger et al, 2011;Bytingsvik et al, 2013;Simon et al, 2013;Gabrielsen et al, 2015). The effects of EDCs on thyroid hormones appear to be particularly pronounced in female and subadult polar bears, whereas adult males appear to be much more resistant (Braathen et al, 2004;Villanger et al, 2011).…”

Polar bears: proceedings of the 18th working meeting of the IUCN/SSC Polar Bear Specialist Group, Anchorage, Alaska, 7-11 June 2016

“…Gutleb et al (2010) extracted thyroid transporting proteins from polar bear plasma and found that one of the major OH-PCBs in polar bear plasma has much higher affinity towards transthyretin (TTR) than its natural ligand thyroxine. The study suggested that TTR in free-ranging polar bears are completely saturated by contaminants.…”

Barents Sea polar bears (Ursus maritimus): population biology and anthropogenic threats

“…Arctic organisms are adapted to dealing with short periods of high production during which lipid energy stores are built up, resulting in high dependence on fat at most trophic levels (Barrie et al 1992). Polar bears have the capacity to metabolize several organic pollutants (Letcher et al 2000), but the metabolites resulting from this process are believed to have an even more negative effect than the original compounds (Cheek et al 1999;Marchesini et al 2008;Gutleb et al 2010). …”