Inhibition of intrathyroidal dehalogenation by iodide.
Iodide is a trace element and a key component of thyroid hormones (TH). The availability of this halogen is the rate-limiting 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.
Department of Biomedical Research, School of Medicine, Autonomous University of Queretaro, Clavel 200, Queretaro, Queretaro 76017, Mexico. carlos.solis@uaq.mx
Juan C
JC
Solis-S
Patricia
P
Villalobos
Aurea
A
Orozco
Guadalupe
G
Delgado
Andres
A
Quintanar-Stephano
Pablo
P
Garcia-Solis
Hebert L
HL
Hernandez-Montiel
Ludivina
L
Robles-Osorio
Carlos
C
Valverde-R
D000704:Analysis of Variance; D000818:Animals; D006867:Hydrolases / Q000235:genetics / Q000378:metabolism*; D007016:Hypophysectomy; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism*; D007454:Iodides / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027981:Symporters / Q000235:genetics / Q000378:metabolism; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism*; D013972:Thyrotropin / Q000378:metabolism / Q000494:pharmacology; D013974:Thyroxine / Q000378:metabolism / Q000494:pharmacology; D014284:Triiodothyronine / Q000378:metabolism / Q000494:pharmacology; D000099209:Sodium-Iodide Symporters
D006867:Hydrolases; D007453:Iodide Peroxidase; D007454:Iodides; D012333:RNA, Messenger; D027981:Symporters; D013972:Thyrotropin; D013974:Thyroxine; D014284:Triiodothyronine; D000099209:Sodium-Iodide Symporters; C109812:iodothyronine deiodinase type I; C487688:iodotyrosine dehalogenase, rat