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Endocrinology, Vol 114, 1379-1385, Copyright © 1984 by Endocrine Society


ARTICLES

Autoregulation by iodine of thyroid protein synthesis: influence of iodine on amino acid transport in cultured thyroid cells

S Filetti and B Rapoport

Studies were conducted to determine whether the inhibitory effect of iodine on thyroid protein synthesis could be explained by a reduction in intracellular amino acid transport. The nonmetabolizable amino acid [14C]cycloleucine was used as a probe for the L system of neutral amino acid transport in dog thyroid cells during the initial 24 h of primary culture. Uptake of cycloleucine was linear for up to 30 min. At all time points, cycloleucine transport was reduced in cells preincubated for 3 h in NaI (10(-4) M). Inhibition (in a typical experiment) by NaI of cycloleucine transport (10 min) was 19%, 42%, and 69% at 10(-6), 10(- 5), and 10(-4) M iodide, respectively. Methimazole (3 mM) together with iodide abolished the inhibitory effect of iodide on cycloleucine transport, implying the necessity of iodide organification. Methimazole itself did not significantly alter cycloleucine transport. T3, T4, MIT, and DIT similarly did not inhibit cycloleucine transport. NaI did not inhibit cycloleucine transport in cells lacking a mechanism for iodide organification. Double reciprocal plots of cycloleucine influx at different substrate concentrations indicated that NaI decreases the maximum velocity of cycloleucine transport (2.1 vs. 4.0 nmol min-1 mg protein-1) without affecting the Km (1 mM). In contrast to influx, iodine did not affect cycloleucine efflux. The inhibitory action of iodine on cycloleucine transport was reversible after removal of extracellular iodide, with full recovery occurring within 24 h. Iodine similarly inhibited the cellular uptake of [14C] alpha- methylaminoisobutyric acid as well as [14C] alpha-aminoisobutyric acid in the presence of 30 mM methyl-alpha-aminoisobutyric acid, that is of specific probes for the A and ASC transport systems of neutral amino acids, respectively. These data indicate that autoregulation by iodine of thyroid protein synthesis occurs, at least in part, by regulation of the maximum velocity of neutral amino acid uptake via the A, ASC, and L transport systems.





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