Excess iodide decreases transcription of NIS and VEGF genes in rat FRTL-5 thyroid cells.
Although it is well known that an excess of iodide suppresses thyroid function and blood flow in vivo, the underlying molecular mechanisms are not fully known. The functional effect of iodide occurs at multiple steps, which include inhibition of sodium/iodide symporter (NIS) expression, transient block of organification, and inhibition of hormonal release. The vascular effect likely involves suppression of the vascular endothelial growth factor (VEGF) gene. In this report, we show that excess iodide coordinately suppresses the expression of the NIS and VEGF genes in FRTL-5 thyroid cells. We also demonstrate that the mechanism of iodide suppression of NIS gene expression is transcriptional, which is synergized by the addition of thyroglobulin. Based on the findings of reporter gene assays and electrophoretic gel mobility shift analysis, we also report two novel DNA binding proteins that responded specifically to iodide and modulated NIS promoter activity. The results suggest that excess iodide affects thyroid vascular function in addition to iodide uptake. This study provides additional insights into the mechanism of action of excess iodide on thyroid function.
Suzuki
Koichi
K
Leprosy Research Center, National Institute of Infectious Diseases, Tokyo, Japan. koichis@nih.go.jp
Kimura
Hiroaki
H
Wu
Huhehasi
H
Kudo
Naoko
N
Kim
Won Bae
WB
Suzuki
Sayuri
S
Yoshida
Akio
A
Caturegli
Patrizio
P
Kohn
Leonard D
LD
D000818:Animals; D002460:Cell Line; D024202:Electrophoretic Mobility Shift Assay; D007454:Iodides / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D027981:Symporters / Q000037:antagonists & inhibitors / Q000235:genetics*; D013954:Thyroglobulin / Q000378:metabolism / Q000494:pharmacology; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000235:genetics*; D000099209:Sodium-Iodide Symporters
D007454:Iodides; D027981:Symporters; D013954:Thyroglobulin; D042461:Vascular Endothelial Growth Factor A; D000099209:Sodium-Iodide Symporters; C467498:vascular endothelial growth factor A, rat