Pendred syndrome is an autosomal recessive disorder characterized by congenital 
deafness and thyroid goiter. The thyroid disease typically develops around 
puberty and is associated with a mild organification defect, characterized by an 
inappropriate discharge of iodide upon perchlorate stimulation (a positive 
perchlorate discharge test). The gene (PDS) mutated in Pendred syndrome is 
expressed in thyroid and encodes a 780-amino acid protein (pendrin) that has 
recently been shown to function as an iodide/chloride transporter. We sought to 
establish the location of pendrin in the thyroid and to examine the regulatory 
network controlling its synthesis. Using peptide-specific antibodies for 
immunolocalization studies, pendrin was detected in a limited subset of cells 
within the thyroid follicles, exclusively at the apical membrane of the 
follicular epithelium. Interestingly, significantly greater amounts of pendrin 
were encountered in thyroid tissue from patients with Graves' disease. Using a 
cultured rat thyroid cell line (FRTL-5), PDS expression was found to be 
significantly induced by low concentrations of thyroglobulin (TG), but not by 
TSH, sodium iodide, or insulin. This is different from the established effect of 
TG, more typically a potent suppressor of thyroid-specific gene expression. 
Together, these results suggest that pendrin is an apical porter of iodide in 
the thyroid and that the expression and function of both the apical and basal 
iodide porters are coordinately regulated by follicular TG.