Effects of 3-nitro-<sc>l</sc>-tyrosine on thyroid function in the rat: an experimental model for the dehalogenase defect

William L. Green

doi:10.1172/JCI106748

Effects of 3-nitro-l-tyrosine on thyroid function in the rat: an experimental model for the dehalogenase defect

William L. Green

Published December 1, 1971 - More info

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Abstract

The effects on thyroid function of an inhibitor of tyrosine dehalogenase, 3-nitro-L-tyrosine (MNT) have been investigated in rats. In preliminary studies, marked inhibition of iodotyrosine deiodination was demonstrated in rats drinking 8 mM MNT. A series of experiments was then performed in which rats received Remington low iodine diet and 8 mM MNT as drinking fluid. This regimen had the following effects, compared to the effects of a low iodine diet alone: (a) a decrease in serum protein-bound iodine, elevation of serum thyrotropin level, goiter, and growth inhibition all prevented or reversed by iodine supplements: (b) on initiation of MNT, a 2- to 3-fold increase in the rate of release of radioiodine from the thyroid and concomitant urinary excretion of large amounts of organic iodine: and (c) after 2 wk of MNT, a greatly increased rate of thyroidal uptake and release of ¹³¹I, an increase in the ratio of monoiodotyrosine-¹³¹I to diiodotyrosine-¹³¹I in thyroid proteolysates and the appearance of labeled iodotyrosines in serum.

Acute administration of MNT intraperitoneally to rats on either an iodine-deficient or iodine-sufficient diet did not inhibit thyroidal uptake of ¹³¹I or alter the distribution of ¹³¹I among thyroidal iodoamino acids.

It is concluded that MNT is an effective inhibitor of iodotyrosine deiodination in vivo, without other important actions on thyroid function. Thus, MNT treatment affords a model for the human dehalogenase defect. By provoking iodotyrosine secretion and consequent urinary loss of iodine, MNT can exaggerate the effects of a low iodine intake, producing goitrous hypothyroidism despite a rapid rate of iodine turnover in the thyroid.

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