Iodide inhibits vascular endothelial growth factor-A expression in cultured human thyroid follicles: a microarray search for effects of thyrotropin and iodide on angiogenesis factors.
OBJECTIVE
Excess iodide has been administered to hyperthyroid patients before thyroid surgery to reduce intraoperative bleeding and oozing. The purpose of this study was to elucidate the mechanism by which iodide reduces blood flow in the hypervascular thyroid gland.


METHODS
Human thyroid follicles were cultured in the presence or absence of thyrotropin (TSH), or in medium containing various concentrations of iodide, and TSH-or iodide-regulated gene expression was analyzed by cDNA microarray.


RESULTS
TSH stimulated the expression of thyroglobulin, peroxidase, sodium iodide symporter, vascular endothelial growth factor (VEGF)-A, VEGF-B, and placental growth factor (PGF) but decreased that of VEGF-C by half. When thyroid follicles were cultured in high-iodide (10(5) M) medium, TSH-induced expression of VEGF-A, VEGF-B, and PGF was decreased, accompanied by a reduction of VEGF-A release into the medium. Furthermore, expression of putative angiogenesis inhibitors such as urokinase-type plasminogen activator (PLAU) was increased. These findings were confirmed by real-time polymerase chain reaction (PCR) and Northern blot hybridization.


CONCLUSIONS
We have demonstrated for the first time that iodide at high concentration decreases the expression of the angiogenic factors VEGF-A, VEGF-B, and PGF, accompanied by an increase in the expression of possible antiangiogenic factors such as PLAU. These proangiogenic and antiangiogenic factors may at least partly account for the iodide-induced decrease in thyroid blood flow.
Yamada
Emiko
E
Thyroid Disease Institute, Kanaji Hospital, Tokyo, Japan.
Yamazaki
Kazuko
K
Takano
Kazue
K
Obara
Takao
T
Sato
Kanji
K
D015152:Blotting, Northern; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D006111:Graves Disease / Q000378:metabolism; D006801:Humans; D007454:Iodides / Q000378:metabolism* / Q000494:pharmacology*; D009389:Neovascularization, Pathologic; D020411:Oligonucleotide Array Sequence Analysis; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000096:biosynthesis*; D013961:Thyroid Gland / Q000378:metabolism*; D013972:Thyrotropin / Q000378:metabolism*; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D042561:Vascular Endothelial Growth Factor B / Q000096:biosynthesis*
D007454:Iodides; C000608036:PGF protein, human; D011257:Pregnancy Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042561:Vascular Endothelial Growth Factor B; D000072483:Placenta Growth Factor; D013972:Thyrotropin