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 (131)I, an increase in the ratio of monoiodotyrosine-(131)I to diiodotyrosine-(131)I 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 (131)I or alter the distribution of (131)I 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.