title: Effects of iodotyrosine deiodinase inhibition on serum concentrations and turnover of diiodotyrosine (DIT) and thyroxine (T4) in the rat.
abstract: 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.
mesh_terms: D000818:Animals; D004105:Diiodotyrosine / Q000097:blood*; D005260:Female; D007453:Iodide Peroxidase / Q000378:metabolism*; D007700:Kinetics; D008657:Metabolic Clearance Rate / Q000187:drug effects; D010544:Peroxidases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013974:Thyroxine / Q000097:blood*; D014284:Triiodothyronine / Q000097:blood; D014285:Triiodothyronine, Reverse / Q000097:blood; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D014284:Triiodothyronine; C002744:3-nitrotyrosine; D014443:Tyrosine; D014285:Triiodothyronine, Reverse; D004105:Diiodotyrosine; D010544:Peroxidases; D007453:Iodide Peroxidase; D013974:Thyroxine