REGULATION OF TRANSFORMING-GROWTH-FACTOR BETA(1) MESSENGER-RIBONUCLEIC-ACID EXPRESSION IN PORCINE THYROID-FOLLICLES IN-VITRO BY GROWTH-FACTORS, IODINE, OR DELTA-IODOLACTONE

Transforming growth factor beta(1) (TGF beta(1)) is an autocrine growt h factor for thyrocytes and is supposed to be the mediator of iodine-i nduced growth inhibition of thyroid epithelial cells, but this is stil l controversial. We further investigated this hypothesis using intact porcine thyroid follicles ex vivo in a three-dimensional culture syste m. In this culture system it has been shown previously that both iodid e as well as delta-iodolactone, the putative iodocompound mediating th yroid cell proliferation, inhibit growth of these follicles. We measur ed the amount of TGF beta(1) mRNA expression in these follicles after treatment either with thyrotropin (TSH), epidermal growth factor (EGF) , or transforming growth factor alpha (TGF alpha) for growth stimulati on or with inorganic iodine or delta-iodolactone in concentrations kno wn to inhibit growth. TGF beta(1)-mRNA was detected by Northern blot a nalysis. The known major transcript of 2.5 kb was detected in a steady state level up to 48 hours in untreated thyroid follicles. EGF and TG F alpha (5 ng/mL each) enhanced TGF beta(1) mRNA about threefold withi n 4 and 8 hours. This increase of TGF beta(1) mRNA was slightly decrea sed by simultaneous incubation with delta-iodolactone (1 mu M) or iodi de (40 mu M KI). In contrast, both TSH (1 mU/mL) and forskolin (16 mu M) decreased TGF beta(1) mRNA expression to about 70%, and this effect was abolished when follicles were pretreated with iodide (40 mu M KI) in a concentration known to inhibit TSH action on cyclic adenosine mo nophosphate (cAMP) formation and proliferation. Iodide or delta-iodola ctone alone had no significant effect on basal TGF beta(1) mRNA expres sion. We conclude that the growth inhibitory effect of iodide as well as of delta-iodolactone is not mediated through TGF beta(1) in intact porcine thyroid follicles ex vivo. The stimulatory effect of EGF and T GF alpha on TGF beta(1) expression might be related to extracellular m atrix modulation during proliferation.