Thyroid hormones are essential for normal development and metabolism. Their 
synthesis requires transport of iodide into thyroid follicles. The mechanisms 
involving the apical efflux of iodide into the follicular lumen are poorly 
elucidated. The discovery of mutations in the SLC26A4 gene in patients with 
Pendred syndrome (congenital deafness, goiter, and defective iodide 
organification) suggested a possible role for the encoded protein, pendrin, as 
an apical iodide transporter. We determined whether TSH regulates pendrin 
abundance at the plasma membrane and whether this influences iodide efflux. 
Results of immunoblot and immunofluorescence experiments reveal that TSH and 
forskolin rapidly increase pendrin abundance at the plasma membrane through the 
protein kinase A pathway in PCCL-3 rat thyroid cells. The increase in pendrin 
membrane abundance correlates with a decrease in intracellular iodide as 
determined by measuring intracellular (125)iodide and can be inhibited by 
specific blocking of pendrin. Elimination of the putative protein kinase A 
phosphorylation site T717A results in a diminished translocation to the membrane 
in response to forskolin. These results demonstrate that pendrin translocates to 
the membrane in response to TSH and suggest that it may have a physiological 
role in apical iodide transport and thyroid hormone synthesis.