NITRIC OXIDE INHIBITS THYROPEROXIDASE (TPO) GENE EXPRESSION AT TRANSCRIPTIONAL LEVEL BY INVOLVING TTF-2 THYROID TRANSCRIPTION FACTOR IN FRTL-5 CELLS.

LUCERO, ARIEL MAXIMILIANO; VÉLEZ, MARIA LAURA; FOZZATTI, LAURA; NICOLA, JUAN PABLO; PELLIZAS, CLAUDIA GABRIELA; COLEONI, ALDO HECTOR; MASINI-REPISO, ANA MARIA

Buenos Aires.

Congreso; 13th INTERNATIONAL THYROID CONGRESS; 2005

Sociedad Latinoamericana de Tiroides (SLAT), AOTA, ATA y ETA.

Nitric oxide (NO) is a signaling molecule with a variety of biological actions that is released in immune processes. Our previous data indicated that the NO donor, sodium nitroprusside (SNP), inhibited iodide uptake and decreased TPO and thyroglobulin mRNA expression in FRTL-5 thyroid cells. The aims of this study were to further explore the inhibitory role of NO on iodide uptake and to analyze the mechanism involved in the reduction of TPO gene expression induced by NO in TSH (0.5mIU/ml) stimulated FRTL-5 cells. The inhibitory action of NO on iodide uptake was corroborated by using the physiologically active NO donor S-Nitroglutathione (GSNO). In TSH treated FRTL-5 cells transfected with minimal TPO promoter linked to luciferase reporter gene (p420TPOLuc), SNP (12h) decreased transcriptional activity in a concentration-dependent manner. Since TTF-2 is a crucial transcription factor involved in TSH regulation of TPO gene expression, the functional activity of 12ZLuc, a construct containing 12 tandem repeats of Z site (TTF-2 binding site) was assayed. Preliminary data indicated a reduction of TTF-2 mRNA level (Norther blot)  in SNP treated cells (24h). This study supports an inhibitory action of NO on thyroid cell function which could be implied in thyroid pathophysiology. It is revealed for the first time the ability of NO to reduce a thyroid specific gene expression, TPO, at transcriptional level possibly involving TTF-2 transcription factor.