Mechanisms of a reduction of thyroid hormone levels in response to 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin in aryl hydrocarbon receptor-null mice and transthyretin-null mice

摘要: Introduction: We have previously shown that the gestational and lactational exposure to 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) perturbs thyroid hormone homeostasis, followed by hyperplasia of the thyroid in offspring. The most consistent toxic effect of dioxins on thyroid hormone metabolism is the decreased level of thyroxine (T4) in serum. The increase in biliary excretion of T4-glucuronide through induction of UDP-glucuronosyltransferase-1 (UGT-1) by dioxins is thought to be responsible for this reduction. However, the higher affinity of transthyretin (TTR), a major T4-binding protein, not only for PCBs but also for dioxin may contribute to reduced serum T4. To investigate the mechanism of this reduction after TCDD exposure, aryl hydrocarbon receptor (AhR)-null mice (AhR-/-) and TTR-null mice (TTR-/-) were utilized.Materials and Methods: AhR heterozygous (AhR+/-) pregnant mice were dosed at 10 ug …