We examined TGF-β mRNA levels in primary sheep thyroid cell cultures to determine whether the inhibitory effects of iodide on thyroid cells could be explained by an induction of TGF-β mRNA and if this induction was mediated by iodine organification. Thyroid cells were incubated with TSH and five additives (insulin, somatostatin, growth hormone, transferrin, and glycyl-L-histidyl-L-lysin) for 2-3 weeks and then were exposed to sodium iodide (Nal) or 1-methylimidazole-2-thiol (methimazole, MMI), or both for 72 h. Iodide at 10-6
M and 10-4 M significantly increased the amount of TGF-β mRNA as determined by Northern blot analysis with a rat TGF-β1 cDNA probe. This increase in TGF-β1 mRNA was abolished'by the addition of methimazole, an inhibitor of organification. These data indicate that the effects of iodide on thyroid growth and function may be mediated by a process that involves organification of iodide and increases in TGF-β1 mRNA levels.