In an attempt to study intrinsic regulatory mechanism involved in iodine metabolism, chronic and acute effects of TSH, PGE2 and DBC on iodine uptake, iodide discharge and organic binding of iodine were examined using cultured porcine thyroid cells.
Culture in the presence of TSH, PGE2 and DBC for 6 days maintained the ability of thyroid cells to take up iodide and organify it, but culture in the absence of these substances failed to do so. When incubated with Nal in the presence of 1 mm methylmercaptoimidazole (MMI), the cells took up iodide and this accumulated iodide was discharged by TSH, PGE2 and DBC. TSH-, PGE2- and DBC-stimulated iodide discharge was depressed greatly after chronic exposure to TSH, PGE2 or DBC. This refractoriness of TSH-, PGE2- or DBC-stimulated iodide dishcarge was not specific for each thyroid stimulating substance; previous exposure to TSH, PGE2 or DBC induced refractoriness of TSH-, PGE2- and DBC-stimulated iodide discharge, providing evidence for the existence of refractoriness at the level of cyclic AMP action on iodide discharge. When incubated with Nal in the absence of MMI, the cells took up iodide and organified it. After 30 min incubation with Nal, TSH, PGE2 and DBC were added and they stimulated iodide organification further. This TSH-, and PGE2-stimulated iodide organification was also depressed after exposure to TSH or PGE2.
These data indicate that, as an intrinsic regulatory mechanism, refractoriness is operating at the level of cAMP action on iodine discharge and organification.