The Role of Polyhalogenated Aromatic Hydrocarbons on Thyroid Hormone Disruption and Cognitive Function: A Review

2004 ◽  
Vol 27 (4) ◽  
pp. 405-424 ◽  
Author(s):  
T. L. Builee ◽  
J. R. Hatherill
Keyword(s):  
Cognitive Function ◽  
Thyroid Hormone ◽  
Aromatic Hydrocarbons ◽  
Polyhalogenated Aromatic Hydrocarbons

scholarly journals Induction of biotransformation enzymes by polyhalogenated aromatic hydrocarbons (PHAHs):potential impact on animal physiology and health

1999 ◽  
pp. 209-221
Author(s):  
Abraham Brouwer
Keyword(s):  
Thyroid Hormone ◽  
Vitamin A ◽  
Thyroid Hormones ◽  
Aromatic Hydrocarbons ◽  
Recent Observation ◽  
Biological Activities ◽  
Phenolic Metabolites ◽  
Biotransformation Enzymes ◽  
Polyhalogenated Aromatic Hydrocarbons

Biotransformation and its role in the elimination of polyhalogenated aromatic hydrocarbons (PHAHs) has been the subject of many studies from the late seventies onwards. The notion of specific, high affinity interactions of phenolic PHAH metabolites with the plasma transport proteins of thyroid hormone and vitamin A, both in vitro and in vivo, stimulated further research into the possible role of biotransformation in the toxicity of certain PHAHs such as PCBs. Currently, phenolic metabolites of PCBs and related compounds have been identified as major metabolites in blood plasma of e.g. grey seals (Halichoerus grypus) and humans with background environmental exposure to these chemicals. The concentrations of the hydroxy-PCBs were in the same range as the most persistent parent congeners, such as PCB 153, 138 and 180. These phenolic metabolites were found to possess a specific range of biological activities, which differed from the parent compounds. Another potential adverse effect associated with persistent induction of biotransformation enzymes, like UDP-glucuronyl transferases (UGTs) by PHAHs, is a long-term enhanced elimination of several important endogenous ligands such as vitamin A and thyroid hormones. Reduced levels of vitamin A and thyroid hormones have been reported in most experimental animal and wildlife species exposed to PHAHs. The recent observation of the accumulation of high levels of phenolic PCB metabolites in blood and brain of late gestational rat foetuses, in parallel with reductions in both vitamin A and thyroid hormone levels, suggests that these metabolites may play an important role in the observed developmental toxicity of PHAHs

scholarly journals Predictive Modeling of a Mixture of Thyroid Hormone Disrupting Chemicals That Affect Production and Clearance of Thyroxine

2009 ◽  
Vol 28 (5) ◽  
pp. 368-381 ◽  
Author(s):  
J. L. Flippin ◽  
J. M. Hedge ◽  
M. J. DeVito ◽  
G. A. LeBlanc ◽  
K. M. Crofton
Keyword(s):  
Thyroid Hormone ◽  
Predictive Modeling ◽  
Aromatic Hydrocarbons ◽  
Complex Mixtures ◽  
Chemical Data ◽  
Model Predictions ◽  
Single Chemical ◽  
Polyhalogenated Aromatic Hydrocarbons ◽  
Long Evans

Thyroid hormone (TH) disrupting compounds interfere with both thyroidal and extrathyroidal mechanisms to decrease circulating thyroxine (T4). This research tested the hypothesis that serum T4 concentrations of rodents exposed to a mixture of both TH synthesis inhibitors (pesticides) and stimulators of T4 clearance in the liver (polyhalogenated aromatic hydrocarbons, PHAHs) could be best predicted by an integrated addition model. Female Long-Evans rats, 23 days of age, were dosed with dilutions of a mixture of 18 PHAHs (2 dioxins, 4 dibenzofurans, and 12 PCBs, including dioxin-like and non-dioxin like PCBs) and a mixture of 3 pesticides (thiram, pronamide, and mancozeb) for four consecutive days. Serum was collected 24 hours after the last exposure and T4 concentrations were measured by radioimmunoassay. Animals exposed to the highest dose of the mixture experienced a 45% decrease in serum T4. Three additivity model predictions (dose addition, effect addition, and integrated addition) were generated based on single chemical data, and the results were compared. Effect addition overestimated the effect produced by the combination of all 21 chemicals. The results of the dose- and integrated-addition models were similar, and both provided better predictions than the effect-addition model. These results support the use of dose- and integrated additivity models in predicting the effects of complex mixtures.

Thyroid hormone-catecholamine interrelationships during exposure to cold

1981 ◽  
Vol 97 (1) ◽  
pp. 91-97 ◽  
Author(s):  
H. Storm ◽  
C. van Hardeveld ◽  
A. A. H. Kassenaar
Keyword(s):  
Nervous System ◽  
Plasma Concentration ◽  
Thyroid Hormone ◽  
Sympathetic Nervous System ◽  
Plasma Levels ◽  
Surgical Procedure ◽  
Exposure To Cold ◽  
Basal Plasma ◽  
Sympathetic Nervous

Abstract. Basal plasma levels for adrenalin (A), noradrenalin (NA), l-triiodothyronine (T3), and l-thyroxine (T4) were determined in rats with a chronically inserted catheter. The experiments described in this report were started 3 days after the surgical procedure when T3 and T4 levels had returned to normal. Basal levels for the catecholamines were reached already 4 h after the operation. The T3/T4 ratio in plasma was significantly increased after 3, 7, and 14 days in rats kept at 4°C and the same holds for the iodide in the 24-h urine after 7 and 14 days at 4°C. The venous NA plasma concentration was increased 6- to 12-fold during the same period of exposure to cold, whereas the A concentration remained at the basal level. During infusion of NA at 23°C the T3/T4 ratio in plasma was significantly increased after 7 days compared to pair-fed controls, and the same holds for the iodide excretion in the 24-h urine. This paper presents further evidence for a role of the sympathetic nervous system on T4 metabolism in rats at resting conditions.

Biological activity of novel thyroid hormone analogues: role of Na+ taurocholate cotransporting polypeptide in liver selectivity

2015 ◽  
Author(s):  
Giulia Brigante ◽  
Bo Carlsson ◽  
Simone Kersseboom ◽  
Robin P Peeters ◽  
Theo J Visser
Keyword(s):  
Biological Activity ◽  
Thyroid Hormone

scholarly journals Minireview: Thyroid Hormone Transporters: The Knowns and the Unknowns

2011 ◽  
Vol 25 (1) ◽  
pp. 1-14 ◽  
Author(s):  
W. Edward Visser ◽  
Edith C. H. Friesema ◽  
Theo J. Visser
Keyword(s):  
Thyroid Hormone ◽  
Organic Anion ◽  
Psychomotor Retardation ◽  
Cellular Level ◽  
Monocarboxylate Transporter ◽  
Causative Role ◽  
Organic Anion Transporting Polypeptide ◽  
Neurological Abnormalities ◽  
Knockout Animals

The effects of thyroid hormone (TH) on development and metabolism are exerted at the cellular level. Metabolism and action of TH take place intracellularly, which require transport of the hormone across the plasma membrane. This process is mediated by TH transporter proteins. Many TH transporters have been identified at the molecular level, although a few are classified as specific TH transporters, including monocarboxylate transporter (MCT)8, MCT10, and organic anion-transporting polypeptide 1C1. The importance of TH transporters for physiology has been illustrated dramatically by the causative role of MCT8 mutations in males with psychomotor retardation and abnormal serum TH concentrations. Although Mct8 knockout animals have provided insight in the mechanisms underlying parts of the endocrine phenotype, they lack obvious neurological abnormalities. Thus, the pathogenesis of the neurological abnormalities in males with MCT8 mutations is not fully understood. The prospects of identifying other transporters and transporter-based syndromes promise an exciting future in the TH transporter field.

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