Abstract
Transforming growth factor β1 (TGFβ1) is an autocrine growth factor for thyrocytes and is supposed to be the mediator of iodine-induced growth inhibition of thyroid epithelial cells, but this is still controversial. We further investigated this hypothesis using intact porcine thyroid follicles ex vivo in a three-dimensional culture system. In this culture system it has been shown previously that both iodide as well as δ-iodolactone, the putative iodocompound mediating thyroid cell proliferation, inhibit growth of these follicles. We measured the amount of TGFβ1 mRNA expression in these follicles after treatment either with thyrotropin (TSH), epidermal growth factor (EGF), or transforming growth factor α (TGFα) for growth stimulation or with inorganic iodine or δ-iodolactone in concentrations known to inhibit growth. TGFβ1-mRNA was detected by Northern blot analysis. 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 TGFα (5 ng/mL each) enhanced TGFβ1 mRNA about threefold within 4 and 8 hours. This increase of TGFβ1 mRNA was slightly decreased by simultaneous incubation with δ-iodolactone (1 μM) or iodide (40 μM KI). In contrast, both TSH (1 mU/mL) and forskolin (16 μM) decreased TGFβ1 mRNA expression to about 70%, and this effect was abolished when follicles were pretreated with iodide (40 μM KI) in a concentration known to inhibit TSH action on cyclic adenosine monophosphate (cAMP) formation and proliferation. Iodide or δ-iodolactone alone had no significant effect on basal TGFβ1 mRNA expression.
We conclude that the growth inhibitory effect of iodide as well as of δ-iodolactone is not mediated through TGFβ1 in intact porcine thyroid follicles ex vivo. The stimulatory effect of EGF and TGFα on TGFβ1 expression might be related to extracellular matrix modulation during proliferation.
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