The Actions of Iodide and TSH on Thyroid Cells Showing a Dual Control System for the Iodide Pump

In dispersed thyroid cells, iodide concentrating activity was depressed as much as 70% following preincubation with iodide (4 to 60 µM). This effect of iodide appears to represent an in vitro counterpart of the autoregulation of iodide transport that has been observed in rats and mice given injections of iodide. The depression of iodide accumulation was increased in proportion to the duration of the preincubation, to the iodide concentration used, and to the magnitude of iodoprotein formation during the preincubation. It was completely abolished by methimazole present during the preincubation. The depression of iodide concentrating activity induced by iodide was attributable to decreases in the rate constant for unidirectional iodide influx without alteration in the iodide efflux process, so that at any particular concentration of iodide in the medium, the rate of iodide influx was lower in iodide pretreated cells than in the corresponding control cells. This depression of the influx process was associated with increases in the Km rather than decreased Vmax of iodide pump activity. In contrast, preincubation of the cells with TSH induced increases in iodide pump activity that were accounted for by increases in Vmax without change in Km. In studying the interactions between these divergent influences of iodide and TSH, we found that when TSH was added during the preincubation of thyroid cells with iodide, the depression of iodide concentrating activity induced by the iodide was greatly augmented. On the other hand, the pretreatment with iodide not only depressed iodide pump activity, but diminished the stimulatory effect of TSH added thereafter. These findings illustrate the functions of a complex dual control system regulating the thyroidal iodide pump, with TSH acting to accelerate it while iodide tends to brake it. (Endocrinology94: 1465, 1974)