Multisite inhibition by ipodate of iodothyronine secretion from perfused dog thyroid lobes

Abstract

Cholecystographic radiocontrast agents interfere with thyroid hormones in several ways. In the present study 1 mM ipodate induced a rapid sustained and reversible inhibition of the secretion of T4, T3, rT3, 3,3'-diiodothyronine, and 3',5'-diiodothyronine from perfused dog thyroid lobes. This effect was not reproduced by infusion of 3 mM iodide and not affected by 2 mM methimazol or 2 mM perchlorate. One millimolar of ipodate inhibited secretion of T4 to 23.7 +/- 2.8% of control (+/- SE, n = 6), 0.3 mM ipodate to 59.6 +/- 3.01 (n = 4), and 0.1 mM ipodate to 80.4 +/- 5.7% of control (n = 4). In search of the site of action in the thyroid of this inhibitory compound it was found that 1 mM ipodate inhibited TSH-induced increase in thyroidal cAMP, cAMP-induced generation of intracellular colloid droplets, and liberation of T4 and T3 from thyroglobulin by acid proteases and peptidases. These processes are those thought to be inhibited during iodide inhibition of thyroid secretion, via gradual formation of an unknown iodine-containing organic intermediate. It is suggested that the inhibition of thyroid secretion observed in the present study is due to structural similarities between ipodate and this putative iodine-containing mediator of the iodide-induced inhibition of thyroid secretion.