The Pax family encodes transcription factors that function during embryogenesis and regulate the temporal and position-dependent differentiation of cells. Pax-8 is expressed in the developing and adult thyroid, the developing secretory system and at lower levels, in the adult kidney. Pax-8 complexes with TTF-1 and TTF-2 to induce thyroid follicular cell differentiation and thyroid hormone biosynthesis by regulating the expression of sodium iodide symporter (NIS), thyroid peroxidase (TPO), thyroglobulin (TG) and the thyrotropin receptor (TSHR). Treatment of FRTL-5 cells with TGFβ1 decreases Pax-8 mRNA levels and Pax-8 DNA binding activity, which suppresses the expression of TG and the formation of thyrocytes. Patients who have autosomal dominant mutations of the Pax-8 gene develop thyroid dysgenesis. The Pax-8 gene produces six isoforms, A to F, that are generated by alternative splicing and differ in their carboxy-terminal regions. The Pax-8 isoforms display different DNA binding capacities and are thought to be functionally distinct. The gene which encodes Pax-8 maps to human chromosome 2q12-q14.
