Studies on the mechanism of acute inhibition of thyroglobulin hydrolysis by iodine.
Iodine in excess is known to acutely inhibit thyroidal secretion. In the present study we have characterized the time course of the iodine effect in vitro and investigated the underlying mechanisms. Labelled thyroid glands were cultured in vitro in medium containing mononitrotyrosine, an inhibitor of iodotyrosine deiodinase. The rate of hydrolysis of labelled thyroglobulin was measured as the proportion of labelled iodotyrosines and iodothyronines recovered at the end of culture and was used as an index of thyroidal secretion. Thyrotrophin (TSH) administered in vivo acutely stimulated the rate of thyroglobulin hydrolysis. Addition of NaI to the culture medium acutely inhibited both basal and TSH-stimulated thyroglobulin hydrolysis. The effect of iodide was demonstrable after 2 h, maximal after 6 h and was not reversible upon removal of iodide. Iodide abolished the dibutyryl cAMP induced stimulation of thyroglobulin hydrolysis. Iodide required organic binding of iodine for its effect but new protein or RNA synthesis was not necessary. The inhibitory effects of iodide and lysosomotrophic agents such as NH4Cl and chloroquin on thyroglobulin hydrolysis were additive suggesting different sites of action. Iodide added in vitro altered the distribution of label in prelabelled thyroglobulin in a way that suggested increased coupling in the thyroglobulin molecule. These data indicate that 1) the iodide effect occurs progressively over a 6 h period, 2) continued presence of iodide is not necessary once the inhibition is established, 3) iodide exerts its action primarily at a post cAMP, prelysosomal site and 4) the effect requires organic binding of iodine, but not new RNA or protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Bagchi
N
N
Shivers
B
B
Brown
T R
TR
D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D005260:Female; D006868:Hydrolysis; D007455:Iodine / Q000494:pharmacology*; D008713:Methimazole / Q000494:pharmacology; D051379:Mice; D012974:Sodium Iodide / Q000494:pharmacology; D013954:Thyroglobulin / Q000378:metabolism*; D013961:Thyroid Gland / Q000378:metabolism*; D013997:Time Factors
D000643:Ammonium Chloride; D003609:Dactinomycin; D008713:Methimazole; D003994:Bucladesine; D002738:Chloroquine; D013954:Thyroglobulin; D007455:Iodine; D003513:Cycloheximide; D012974:Sodium Iodide