TRANSFORMING GROWTH FACTOR-BETA-1 PRODUCTION IN PORCINE THYROID FOLLICULAR CELLS - REGULATION BY INTRATHYROIDAL ORGANIC IODINE

The present studies have demonstrated the production of transforming growth factor-beta1 (TGF-beta1) by porcine thyroid follicular cells (TFCs) maintained in vitro as subconfluent monolayers, and have confirmed a stimulatory effect of iodide on thyroidal TGF-beta1 mRNA and peptide release. RNA extracted from TFCs maintained in the absence of iodide contained a 2.5 kb transcript which hybridized specifically with a cDNA probe for human TGF-beta1, and which showed an approximate doubling in intensity in cells exposed to 10 mumol NaI/l. In the presence of the anti-thyroid thionamide drug methimazole (MMI; 1 mmol/l), the action of iodide on TGF-beta1 mRNA was attenuated, although MMI alone bad no effect on the control level of TGF-beta1 mRNA. The TGF-beta1 peptide content of TFC-conditioned media (TFC-CM) was assessed using the fetal mink lung cell line Mv1Lu, in which activated TGF-beta1 specifically suppresses trichloroacetic acid-precipitable [methyl-H-3]thymidine incorporation. Newly conditioned TFC-CM stimulated [methyl-H-3]thymidine incorporation into Mv1Lu cells, but after heat treatment to inactivate growth stimulators and activate the latent TGF-beta1 component this medium inhibited [methyl-H-3]thymidine incorporation. This inhibitory effect was prevented by immunoadsorption of TFC-CM with a TGF-beta1-neutralizing antiserum, confirming the specificity of the inhibitory response. The inhibitory activity of TFC-CM was increased when the TFCs were preincubated with 10 mumol NaI/l, and lost when TFCs were exposed to In conclusion, TFCs produce TGF-beta1 mRNA and TGF-beta1 peptide, which are both increased by iodide treatment in vitro. The anti-thyroid effects of MMI may, at least in part, be mediated by a decrease in TFC-derived TGF-beta1 production.