Exogenous free iodotyrosine inhibits iodide transport through the sequential intracellular events

Abstract

Nasu M, Sugawara M. Exogenous free iodotyrosine inhibits iodide transport through the sequential intracellular events. Eur J Endocrinol 1944;130:601–7. ISSN 0804–4643 We describe a new function of exogenous iodotyrosine as a regulator of iodide transport. Porcine thyroid follicles in culture were preincubated with 0–20 μmol/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 M Sugawara, Wadsworth VA Hospital (11 IM), Wilshire and Sawtelle Blvds, Los Angeles, CA 90073, USA