EFFECTS OF TRANSFORMING GROWTH-FACTOR-ALPHA (TGF-ALPHA) ON DNA-SYNTHESIS AND THYROTROPIN-INDUCED IODINE-METABOLISM IN CULTURED PORCINE THYROID-CELLS

Transforming growth factor a (TGF-alpha) is a potent mitogen that is s imilar structurally to epidermal growth factor (EGF). As EGF is a pote nt growth stimulator and an inhibitor of iodine metabolism in cultured thyroid cells of several species, we studied whether TGF-alpha has si milar effects using porcine thyroid cells in culture. Recombinant huma n TGF-alpha dose-dependently stimulated DNA synthesis of thyroid cells , with maximal stimulation (eight- to ninefold above basal) occurring at 2 nmol/l. The potency was approximately 50% that of mouse EGF and c orrelated with the ability to compete with EGF for receptor binding, s uggesting that the action of TGF-alpha is mediated by interaction with EGF receptors. When thyroid cells were cultured for 3 days with thyro tropin (TSH) in the presence of TGF-alpha, TSH-induced iodide uptake w as inhibited in a dose-dependent manner. The potency of TGF-alpha agai n was approximately 50% that of EGF. Transforming growth factor a did not inhibit TSH-stimulated cAMP production. Moreover, iodide uptake st imulated by either forskolin or 8-bromo-cAMP also was inhibited by TGF -alpha. Thus, we conclude that TGF-alpha inhibits TSH-induced iodine m etabolism largely by acting at the steps distal to cAMP production. No rthern blot analysis revealed expression of TGF-alpha mRNA in porcine thyroid cells. These observations suggest that TGF-alpha acts as an au tocrine modulator of growth and differentiated functions in porcine th yroid cells.