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Graves' IgG activate upstream enhancer of the sodium/iodide symporter

Ekaterina Breous1, Achim Wenzel, Ulrich Loos

  • 1Abteilung Innere Medizin I, Universität Ulm, Robert-Koch-Strasse 8, D-89081 Ulm, Germany.

Molecular and Cellular Endocrinology
|April 6, 2004
PubMed

Graves' thyroid tissue has been shown to express elevated levels of human sodium/iodide symporter (hNIS) mRNA and protein. In the present work, we demonstrate for the first time that hNIS gene expression in Graves' disease (GD) is up-regulated by Graves' IgG. Here, in transient transfection experiments using FRTL-5 cells, hNIS promoter and enhancer/luciferase construct showed an up to six-fold increase in transcriptional activity after incubation with purified Graves' IgG. Mutation of a CRE site in hNIS enhancer inhibited Graves' IgG response. In addition, mutation of a novel putative regulatory region in hNIS promoter reduced the stimulation three-fold. This discovered putative regulatory sequence might play a role in hNIS up-regulation by Graves' IgG and TSH. The data presented here complement our current knowledge of the pathogenesis of GD and will contribute to a better understanding of mechanisms regulating the thyroid iodide concentrating activity.

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