Regulation of Differentiated Thyroid Function by Iodide: Preferential Inhibitory Effect of Excess Iodide on Thyroid Hormone Secretion in Sheep Thyroid Cell Cultures*

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Abstract
Primary cultures of sheep thyroid cells have been used to study the inhibitory effects of iodide on thyroid function. Under the influence of TSH, iodide was concentrated with a cell to medium ratio of 20. When thyroid hormone secretion was measured from cells cultured without addition of exogenous iodide, preferential T3 secretion was evident. The optimum iodide concentration for T4 and T3 synthesis and secretion was 10-6 M. Prior exposure to 10-5 M or more iodide decreased subsequent iodide transport in a concentration-dependent manner compared to that in cells acutely exposed to iodide. Although cell to medium ratios were decreased, intracelluar iodide concentrations continued to rise with increasing external iodide concentrations, and iodide available for thyroid hormone synthesis was not in limited supply. Iodide concentrations of 10-4 M or greater inhibited iodothyronine synthesis and thyroid hormone secretion, assessed by both assay of trichloroacetic acid-insoluble Na125I activity in cells and RIA of T4 and T3 in the medium and cell layer. An intermediate concentration of 10-5 M iodide had a marked inhibitory effect on T4 and T3 secretion, but iodothyronine formation on thyroglobulin was only slightly affected. Our results suggest a preferential inhibitory effect of elevated iodide concentrations on thyroid hormone secretion. The adaptive advantages of this selective inhibition would allow storage of iodothyronines in times of iodide sufficiency while maintaining euthyroidism.