Pax-8 protein levels regulate thyroglobulin gene expression

Pax proteins are transcription factors that control differentiation of seve ral cell types. In adult organisms Pax-8 is expressed in the follicular thy roid cell where it interacts with sequences of thyroglobulin and thyroperox idase promoters. In this study, we provide evidence indicating that Pax-8 p rotein levels regulate thyroglobulin gene transcription. The most critical approach consisted in increasing Pax-8 protein levels by transfecting thyro id cells with a Pax-8 expression vector. In this situation the thyroglobuli n promoter transcriptional activity was significantly increased with respec t to untransfected cells. In contrast, the transfection of thyroid transcri ption factor-1 (TTF-1) expression vector causes a modest decrease of thyrog lobulin promoter activity, rather than an increase. Northern blots of human papillary cancers reveal a significant correlation between Pax-8 and thyro globulin mRNAs. Gel-retardation assays suggest that the mechanism by which the Pax-8 protein levels modulate thyroglobulin promoter activity may occur through competition with TTF-1 for a common binding site. Since we also de monstrate that Pax-8 expression is subjected to TSH control, our data stron gly suggest that Pax-8 protein levels could represent an important determin ant for the regulation of thyroid cells.