Nitric oxide/cGMP signalling inhibits TSH-stimulated iodide uptake and

BAZZARA, LEONARDO; VELEZ, MARIA LAURA; COSTAMAGNA, MARIA; CABANILLAS, ANA MARIA; FOZZATTI, LAURA; LUCERO, ARIEL; PELLIZAS, CLAUDIA; MASINI-REPISO, ANA

THYROID

MARY ANN LIEBERT

Año: 2007 vol. 17 p. 717 - 727

1050-7256

Objective: Nitric oxide (NO) induces morphological and functional alterations in primary cultured thyroid cells. The aim of this paper was to analyze the direct influence of a long-term exposition to NO on parameters of thyroid hormone biosynthesis in FRTL-5 cells.Nitric oxide (NO) induces morphological and functional alterations in primary cultured thyroid cells. The aim of this paper was to analyze the direct influence of a long-term exposition to NO on parameters of thyroid hormone biosynthesis in FRTL-5 cells. Design: Cells were treated with the NO donor, sodium nitroprusside (SNP) for 24–72h.Cells were treated with the NO donor, sodium nitroprusside (SNP) for 24–72h. Main outcome: SNP (50-500ìmol/l) reduced iodide uptake in a concentration-dependent manner. The inhibition of iodide uptake increased progressively with time and matched nitrite accumulation. SNP inhibited TPO and TG mRNA expression in a concentration-dependent manner. SNP enhanced cGMP production. cAMP generation was reduced by a high SNP concentration after 48h. 8-Br-cGMP, a cGMP analogue, inhibited iodide uptake as well as TPO and TG mRNA expression. The cGK inhibitor KT-5823 reversed SNP or 8-Br-cGMP-inhibited iodide uptake. TSH pretreatment for 24-48h prevented SNP-reduced iodide uptake although nitrite levels remained unaffected.SNP (50-500ìmol/l) reduced iodide uptake in a concentration-dependent manner. The inhibition of iodide uptake increased progressively with time and matched nitrite accumulation. SNP inhibited TPO and TG mRNA expression in a concentration-dependent manner. SNP enhanced cGMP production. cAMP generation was reduced by a high SNP concentration after 48h. 8-Br-cGMP, a cGMP analogue, inhibited iodide uptake as well as TPO and TG mRNA expression. The cGK inhibitor KT-5823 reversed SNP or 8-Br-cGMP-inhibited iodide uptake. TSH pretreatment for 24-48h prevented SNP-reduced iodide uptake although nitrite levels remained unaffected. Conclusions: These findings favor a long-term inhibitory role of the NO/cGMP pathway on parameters of thyroid hormone biosynthesis. A novel property of NO to inhibit TPO and TG mRNA expression is supported. The NO action on iodide uptake could involve cGK mediation. The longterm inhibition of steps of thyroid hormonogenesis by NO could be of interest in thyroid pathophysiology.These findings favor a long-term inhibitory role of the NO/cGMP pathway on parameters of thyroid hormone biosynthesis. A novel property of NO to inhibit TPO and TG mRNA expression is supported. The NO action on iodide uptake could involve cGK mediation. The longterm inhibition of steps of thyroid hormonogenesis by NO could be of interest in thyroid pathophysiology.