Activated thyroglobulin possesses a transforming growth factor-β activity

Abstract

Thyroglobulin (Tg), the thyroid hormone precursor, is a major protein component in the thyroid gland and may have other important functions. Here, we show that bovine Tg inhibited 125I-labeled transforming growth factor- β1 (125I-TGF-β1) binding to cell-surface TGF-β receptors in mink lung epithelial cells with an IC50 of ~300 nM. After disuccinimidyl suberate (DSS) modification, reduction/alkylation, treatment with 8 M urea, 0.1% SDS, or acidic pH (pH 4-5), Tg exhibited a ~5-10-fold increase of 125I-TGF- β1 binding inhibitory activity with IC50 of ~30-60 nM. This inhibitory activity was an intrinsic property of the Tg and could not be segregated from Tg protein by 5% SDS-polyacrylamide gel electrophoresis or by immunoprecipitation using antiserum to Tg. Untreated Tg did not affect DNA synthesis but blocked the TGF-β-induced inhibition of DNA synthesis in mink lung epithelial cells. After DSS activation, Tg possessed TGF-β agonist activity and inhibited DNA synthesis of mink lung epithelial cells and rat thyroid cells. The activated Tg also exerted a small but significant TGF-β agonist activity in transcriptional activation of plasminogen activator inhibitor-1. These results suggest that Tg possesses an authentic TGF-β activity which can be induced by chemical modifications and treatments with denaturing agents and acidic pH.