Pendrin, the protein encoded by the Pendred syndrome gene (PDS), is an apical porter of iodide in the thyroid and is regulated by thyroglobulin in FRTL-5 cells

Pendred syndrome is an autosomal recessive disorder characterized by congen ital deafness and thyroid goiter. The thyroid disease typically develops ar ound puberty and is associated with a mild organification defect, character ized by an inappropriate discharge of iodide upon perchlorate stimulation ( a positive perchlorate discharge test). The gene (PDS) mutated in Pendred s yndrome is expressed in thyroid and encodes a 780-amino acid protein (pendr in) that has recently been shown to function as an iodide/chloride transpor ter. We sought to establish the location of pendrin in the thyroid and to e xamine the regulatory network controlling its synthesis. Using peptide-spec ific antibodies for immunolocalization studies, pendrin was detected in a l imited subset of cells within the thyroid follicles, exclusively at the api cal membrane of the follicular epithelium. Interestingly, significantly gre ater amounts of pendrin were encountered in thyroid tissue from patients wi th Graves' disease. Using a cultured rat thyroid cell line (FRTL-5), PDS ex pression was found to be significantly induced by low concentrations of thy roglobulin (TG), but not by TSH, sodium iodide, or insulin. This is differe nt from the established effect of TG, more typically a potent suppressor of thyroid-specific gene expression. Together, these results suggest that pen drin is an apical porter of iodide in the thyroid and that the expression a nd function of both the apical and basal iodide porters are coordinately re gulated by follicular TG.