Exogenous free iodotyrosine inhibits iodide transport through the sequential intracellular events.
We describe a new function of exogenous iodotyrosine as a regulator of iodide transport. Porcine thyroid follicles in culture were preincubated with 0-20 mumol/l monoiodotyrosine or diiodotyrosine (DIT) in the presence of bovine thyrotropin (TSH) for 24 h; these iodotyrosines inhibited iodide uptake in a dose-response manner. Extracellular [125I]DIT was actively transported to the thyroid follicle in the presence of TSH or (Bu)2cAMP. Inhibition of iodide uptake by iodotyrosine required preincubation with iodotyrosine in the presence of TSH; without TSH, iodotyrosine was ineffective. Follicles preincubated with DIT for 24 h inhibited TSH-mediated cAMP production, which is an important signal for iodide transport. Inhibition of iodide uptake and cAMP generation by iodotyrosine was negated characteristically by 3-nitro-L-tyrosine, an inhibitor of iodotyrosine deiodinase, or by methimazole, an inhibitor of thyroid peroxidase. Our findings suggest that iodotyrosine regulates iodide transport through the following sequential intracellular events: TSH-dependent iodotyrosine transport into the thyroid cell; deiodination of iodotyrosine and release in iodide; iodine organification by the peroxidase system; inhibition of cAMP generation by organified iodine; and inhibition of iodide transport. Thus, exogenous iodotyrosine can serve as an inhibitor of thyroid hormone formation only when TSH is present.
Nasu
M
M
Division of Endocrinology and Metabolism, Veterans Affairs Medical Center West Los Angeles, CA.
Sugawara
M
M
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D046508:Culture Techniques; D000242:Cyclic AMP / Q000096:biosynthesis; D004105:Diiodotyrosine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007454:Iodides / Q000378:metabolism*; D007470:Monoiodotyrosine / Q000494:pharmacology*; D013552:Swine; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013972:Thyrotropin / Q000502:physiology
D007454:Iodides; D004105:Diiodotyrosine; D013972:Thyrotropin; D000242:Cyclic AMP; D007470:Monoiodotyrosine