Target tissue toxicity of the thyroid hormone system in two species of arctic mammals carrying high loads of organohalogen contaminants
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- Institutt for biologi 
Background: Arctic marine top predators such as the hooded seals (Cystophora cristata) and polar bears (Ursus maritimus) are exposed to and bioaccumulate high levels of lipophilic organohalogen contaminants (OHCs) through their diets. The physiochemical properties of the specific compounds, biotransformation as well as tissue characteristics result in tissue-specific concentrations and patterns of OHCs. Many of the OHC found in high levels in hooded seals and polar bears have the ability to disrupt the thyroid hormone (TH) system, which is considered to be among one of the most critical targets of endocrine disruption in mammals. Objective: In the current thesis, the possible effects and mechanisms of OHCs on the TH system in hooded seals and polar bears were explored by including endpoints in TH target tissues that previously has not been reported in wildlife studies. This was done by analysing concentrations of THs and deiodinase activities in liver, kidney and muscle tissues in addition to plasma concentrations of THs. The association between these endpoints and plasma as well as tissue-specific concentrations of OHCs were examined. Results and discussion: Circulating levels of OHCs were associated with circulating levels of THs in hooded seals and in polar bears. Polychlorinated biphenyls (PCBs) and hydroxylated PCBs (OH-PCBs) appeared especially important in influencing the circulating TH homeostasis, adding furter weight to the evidence that circulating TH levels are affected by exposure to OHCs in arctic marine mammals. The results in the present thesis also indicate that newborn hooded seal pups have increased susceptibility for TH-disruption by OH-PCBs and/or PCBs. The present thesis has provided a better knowledge of the TH physiology in polar bears by investigating levels of THs deiodinase activities in tissues and explored their relationships with circulating TH concentrations. This is important to better evaluate contaminants-induced effects. Further, concentrations of individual OHCs in plasma were negatively associated with total tetraiodothyrinine (TT4) in skeletal muscle and positively associated with deiodinase activities in liver, kidney and muscle. Sum (∑) BFR in liver tissue was negatively associated with hepatic concentrations of total triiodothyronine (TT3). In addition, PCBs and BFRs appeared to influence the partitioning or regulation of THs across tissues. In summary, the present thesis indicates that effects of OHCs occur on a circulatory level as well as in target tissues of TH functioning and regulation, and that this can be studied using both circulating and tissue-specific concentrations of OHCs. While biomonitoring of plasma concentrations of OHCs are suitable for examining potential circulating and tissue-specific effects on TH-disruption in wildlife studies, tissuespecific concentrations of OHCs might be more appropriate when investigating possible TH-disrupting mechanisms and sensitivities of different tissues or organs. The ice-dependent hooded seals and polar bears both risk climate change-induced habitat loss, predicted to cause negative population effects for both species. As functional endocrine systems are essential for enabling acclimatisation and/or adaptations to a changing climate, exposure to TH-disruptive contaminants may be a worst-case scenario for these arctic species.