Effects of Transforming Growth Factor-β on Deoxyribonucleic Acid Synthesis and Iodine Metabolism in Porcine Thyroid Cells in Culture*

Abstract

The effect of transforming growth factor (TGF)-.beta. on DNA synthesis and iodine metabolism was studied in cultured porcine thyroid cells. TGF-.beta.-dose-dependently inhibited DNA synthesis stimulated by both insulin-like growth factor I and epidermal growth factor but did not affect the number or affinity of receptors for the two growth factors, suggesting that TGF-.beta. inhibits postreceptor events responsible for initiation of DNA synthesis. TGF-.beta. was a potent inhibitor of iodine metabolism. When porcine thyroid cells were cultured with TSH for 3 days in the presence of TGF-.beta., TSH-induced iodide uptake and organification were reduced at rates that were dependent on the TGF-.beta. concentrations. The inhibition was detectable at TGF-.beta. concentrations as low as 50 pg/ml, and complete suppression was seen at 1 ng/ml. Only 6 h of exposure to TGF-.beta. resulted in a significant inhibition of TSH-induced iodine metabolism. Treatment of thyroid cells with TGF-.beta. for 3 days did not reduce cAMP production stimulated by TSH. Moreover, the intracellular cAMP level of thyroid cells cultured with TSH plus TGF-.beta. did not differ from that of cells cultured with TSH alone. TGF-.beta. decreased iodide uptake stimulated by forskolin or 8-bromo-cAMP. These results strongly suggest that TGF-.beta. inhibits TSH-stimulated iodine metabolism, at least in part, by affecting events subsequent to cAMP production. The physiological role of TGF-.beta. remains to be determined, but it may be involved in the regulation of thyroid cell growth and function.