Porcine thyroid follicular cells in monolayer culture activate the iodide-responsive precursor form of transforming...

The release of latent transforming growth factor-beta 1 (TGF-beta 1), and conversion to the biologically active peptide, has been investigated in porcine thyroid follicular cells maintained in primary monolayer culture. Analysis by radioreceptor assay of medium conditioned for 72 h by subconfluent thyroid monolayers showed that a high proportion of the expressed TGF-beta 1 peptide was in the active form. Medium conditioned by iodide (10 mumol/l)-treated follicular cells contained higher levels of both active and total TGF-beta 1 than were present in medium conditioned by untreated cells. Exposure of cells to iodide also led to a marked decrease in [methyl-3H]thymidine incorporation that was relieved by immunoadsorption with a neutralizing antiserum against the active form of TGF-beta 1. Inclusion of a low dose (80 units/l) of porcine plasmin led to a small increase in incorporation of [methyl-3H]thymidine, while higher doses of plasmin (1250-5000 units/l) or plasminogen (100 mg/l) significantly reduced [methyl-3H]thymidine incorporation. This inhibition was effectively reversed by immunoadsorption of TGF-beta 1 from the medium during the test incubations. The study therefore provides direct evidence for a stimulatory role of thyroidal iodide in enhancing the release of latent TGF-beta 1 peptide, and suggests that in normal thyroid follicular cells, as in other TGF-beta 1 producing epithelia, post-secretory processing to the biologically active molecule occurs through an endogenous cellular mechanism. It appears likely that plasmin, generated locally within the thyroid follicular microenvironment, may play a fundamental role in effecting this conversion.