Effects of iodotyrosine deiodinase inhibition on serum concentrations and turnover of diiodotyrosine (DIT) and thyroxine (T4) in the rat.

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.