Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.11.1.8 (thyroid peroxidase)
 3,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum concentrations and metabolic clearance rates (MCR) of diiodotyrosine (DIT) and thyroxine (T4) have been measured by radioimmunoassay and tracer kinetic technique in both normal rats and rats treated with 3-nitro-L-tyrosine (MNT), a potent inhibitor of iodotyrosine deiodinase. In normal rats, DIT serum levels were 0.27 +/- 0.12 nmol/l (mean +/- SD); MCR was 15.9 ml/h . 100 g body weight (bw), and the turnover rate was 4.3 pmol/h . 100 g bw. Inhibition of iodotyrosine deiodination by treatment with 50 mumol MNT per day for 1 week caused a highly significant elevation of DIT serum levels to 4.80 +/- 3.30 nmol/l, a decrease of MCR to 9.0 ml/h . 100 g bw and a ten-fold increase of the DIT turnover rate to 43.2 pmol/h . 100 g bw. Serum concentrations of T4 and T3 decreased slightly, whereas the T4 turnover rate (37.5 vs 37.8 pmol/h . 100 g bw) and rT3 serum levels remained unchanged under MNT treatment. The study demonstrates the presence of measurable DIT serum concentrations in the normal rat. Inhibition of intra- and extrathyroidal iodotyrosine deiodinase leads to a situation in which circulating iodotyrosines play an equally important role in peripheral iodine turnover as the iodothyronines. Since DIT serum levels in normal and enzyme-blocked rats were comparable to those in normal human subjects and patients with iodotyrosine deiodinase defect respectively, MNT-treated rats afford a suitable experimental model for this disease.
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PMID:Effects of iodotyrosine deiodinase inhibition on serum concentrations and turnover of diiodotyrosine (DIT) and thyroxine (T4) in the rat. 661 96

The enzyme iodotyrosine deiodinase (dehalogenase, IYD) catalyzes iodide recycling and promotes iodide retention in thyroid follicular cells. Loss of function or chemical inhibition of IYD reduces available iodide for thyroid hormone synthesis, which leads to hormone insufficiency in tissues and subsequent negative developmental consequences. IYD activity is especially critical under conditions of lower dietary iodine and in low iodine environments. Our objective was to evaluate the toxicological relevance of IYD inhibition in a model amphibian (Xenopus laevis) used extensively for thyroid disruption research. First, we characterized IYD ontogeny through quantification of IYD mRNA expression. Under normal development, IYD was expressed in thyroid glands, kidneys, liver, and intestines, but minimally in the tail. Then, we evaluated how IYD inhibition affected developing larval X. laevis with an in vivo exposure to a known IYD inhibitor (3-nitro-l-tyrosine, MNT) under iodine-controlled conditions; MNT concentrations were 7.4-200 mg/L, with an additional 'rescue' treatment of 200 mg/L MNT supplemented with iodide. Chemical inhibition of IYD resulted in markedly delayed development, with larvae in the highest MNT concentrations arrested prior to metamorphic climax. This effect was linked to reduced glandular and circulating thyroid hormones, increased thyroidal sodium-iodide symporter gene expression, and follicular cell hypertrophy and hyperplasia. Iodide supplementation negated these effects, effectively rescuing exposed larvae. These results establish toxicological relevance of IYD inhibition in amphibians. Given the highly conserved nature of the IYD protein sequence and scarcity of environmental iodine, IYD should be further investigated as a target for thyroid axis disruption in freshwater organisms.
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PMID:Evaluating Iodide Recycling Inhibition as a Novel Molecular Initiating Event for Thyroid Axis Disruption in Amphibians. 3013 36