Inhibition of intrathyroidal dehalogenation by iodide

Abstract

Iodide is a trace element and a key component of thyroid hormones (TH). The availability of this halogen is the ratelimiting step for TH synthesis; therefore, thyroidal iodide uptake and recycling during TH synthesis are of major importance in maintaining an adequate supply. In the rat, the thyroid gland co-expresses a distinctive pair of intrathyroidal deiodinating enzymes: the thyroid iodotyrosine dehalogenase (tDh) and the iodothyronine deiodinase type 1 (ID1). In the present work, we studied the activity of these two dehalogenases in conditions of hypo-and hyperthyroidism as well as during acute and chronic iodide administration in both intact and hypophysectomized (HPX) rats. In order to confirm our observations, we also measured the mRNA levels for both dehalogenases and for the sodium/iodide symporter, the protein responsible for thyroidal iodide uptake. Our results show that triiodothyronine differentially regulates tDh and ID1 enzymatic activities, and that both acute and chronic iodide administration significantly decreases rat tDh and ID1 activities and mRNA levels. Conversely, both enzymatic activities increase when intrathyroidal iodide is pharmacologically depleted in TSH-replaced HPX rats. These results show a regulatory effect by iodide on the intrathyroidal dehalogenating enzymes and suggest that they contribute to the iodide-induced autoregulatory processes involved in the Wolff-Chaikoff effect.

Toxicology of Repeated Iodine Thyroid Blocking in Adult Rat

“…There has been no difference in neither TSH concentration nor plasma thyroid hormone levels observed between treated and control groups, respectively; this may suggest that the thyroid function has not been affected by the repeated administration of iodide. These results are in accordance with other clinical and preclinical studies that reported no impact of iodide on the pituitary-thyroid axis activity [15,21,33,37,[39][40][41][42][43].…”

“…Wolff and Chaikoff demonstrated in 1948 that an excess of iodide in rats may transiently disrupt thyroid function, the well-known Wolff-Chaikoff effect is characterized by a decrease in and delayed iodide organification [18]. This affects many steps of thyroid hormone synthesis and secretion; such iodide entrance and organification, iodide efflux through the colloid, intra-thyroidal iodide pool regeneration, and thyroid hormones transport [19][20][21][22]. This effect could lead to a temporary variation in thyroid hormones level, which exerts a major impact on development, growth, and metabolism [19,22].…”

American Thyroid Association Guide to Investigating Thyroid Hormone Economy and Action in Rodent and Cell Models

“…However, these differences were no longer observed after 3 weeks of treatment (209). A state of hypothyroidism can be achieved faster if PTU or MMI are combined with 1% KClO 4 in the drinking water, a potent NIS inhibitor (210,211). However, their combination will also magnify the effect that these drugs have on water consumption.…”

Iodine-induced thyroid dysfunction

“…Although the mechanism for the acute Wolff–Chaikoff effect remains incompletely understood, it has been hypothesized to be due to the generation of intrathyroidal iodolactones, iodoaldehydes, or iodolipids, which inhibit thyroid peroxidase activity [6,7]. Reduced intrathyroidal deiodinase activity induced by high concentrations of iodine may also contribute to decreased thyroid hormone synthesis [8]. …”