Nitric oxide/cGMP signalling inhibits TSH-stimulated iodide uptake and expression of thyroid peroxidase and thyroglobulin mRNA in FRTL-5 thyroid cells

BAZZARA LG, VÉLEZ ML, COSTAMAGNA ME, CABANILLAS AM, FOZZATTI L, LUCERO AM, PELLIZAS CG, MASINI-REPISO AM.

THYROID

Mary Ann Libert, Inc

Lugar: New York, USA; Año: 2006

1050-7256

Previous reports indicated that nitric oxide (NO) inhibited differentiation characteristics in thyroid follicular cells. The action of NO on the expression of genes related to thyroid hormone biosynthesis has not been explored. This work aimed to analyse the role of the NO/guanylyl cyclase/cyclic GMP (cGMP) pathway on iodide uptake and TPO and thyroglobulin (Tg) gene expression in TSH-stimulated thyroid cells FRTL-5. The NO donor sodium nitroprusside (SNP) inhibited iodide uptake in a concentration (50-500 m mol/l) and time (24-72 h) dependent manner in TSH (500 m U/ml)-stimulated cells. A reduction of TPO and Tg mRNA expression (Northern-blot) after SNP addition was observed. Treatment for 24-48 h with 50-500 m mol/l SNP increased cGMP levels (RIA) in a concentration and time dependent fashion whereas cAMP level (RIA) was decreased by 500 m mol/l SNP at 48 h and was not modified at shorter times and lower SNP concentrations. A significant increase of cGMP was induced by TSH. A reduction of iodide uptake was induced by 1000 m mol/l 8-Br-cGMP The TPO and Tg mRNA expression was significantly reduced by 8-Br-cGMP. The inhibition exerted by SNP or 8-Br-cGMP on iodide uptake was reversed by KT-5823, an inhibitor of the cGMP-dependent protein kinase (PKG). These findings revealed an inhibitory action of NO on thyroid differentiation parameters that could involve cGMP mediation. A reduction in the cAMP production could be relevant in the action of high NO levels. A novel role of the NO/cGMP pathway in the regulation of thyroid specific genes was evidenced.