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

• Published in: Thyroid (New York, N.Y.) Vol. 17; no. 8; p. 717
• Main Authors: Bazzara, Leonardo Gabriel, Vélez, María Laura, Costamagna, María Eugenia, Cabanillas, Ana María, Fozzatti, Laura, Lucero, Ariel Maximiliano, Pellizas, Claudia Gabriela, Masini-Repiso, Ana María
• Format: Journal Article
• Language: English
• Published: United States 01-08-2007
• Subjects: Animals; Carbazoles - pharmacology; Cell Line; Cyclic AMP - metabolism; Cyclic GMP - analogs & derivatives; Cyclic GMP - metabolism; Cyclic GMP - pharmacology; Cyclic GMP-Dependent Protein Kinases - antagonists & inhibitors; Cyclic GMP-Dependent Protein Kinases - metabolism; Gene Expression - drug effects; Gene Expression - physiology; Iodide Peroxidase - genetics; Iodides - pharmacokinetics; Nitric Oxide - metabolism; Nitric Oxide Donors - pharmacology; Nitroprusside - pharmacology; Protein Kinase Inhibitors - pharmacology; Rats; RNA, Messenger - metabolism; Signal Transduction - drug effects; Signal Transduction - physiology; Thyroglobulin - genetics; Thyroid Gland - cytology; Thyroid Gland - metabolism; Thyroid Hormones - biosynthesis; Thyrotropin - metabolism; Thyrotropin - pharmacology
• ISSN: 1050-7256
• DOI: 10.1089/thy.2007.0086

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.
Cells were treated with the NO donor sodium nitroprusside (SNP) for 24-72 h.
SNP (50-500 micromol/L) reduced iodide uptake in a concentration-dependent manner. The inhibition of iodide uptake increased progressively with time and matched nitrite accumulation. SNP inhibited thyroperoxidase (TPO) and thyroglobulin (TG) mRNA expression in a concentration-dependent manner. SNP enhanced 3',5'-cyclic guanosine monophosphate (cGMP) production. 3',5'-cyclic adenosine phosphate (cAMP) generation was reduced by a high SNP concentration after 48 h. 8-Bromoguanosine 3',5'-cyclic monophosphate (8-Br-cGMP), a cGMP analog, inhibited iodide uptake as well as TPO and TG mRNA expression. The cGMP-dependent protein kinase (cGK) inhibitor KT-5823 reversed SNP or 8-Br-cGMP-inhibited iodide uptake. Thyroid-stimulating hormone pretreatment for 24-48 h prevented SNP-reduced iodide uptake although nitrite levels remained unaffected.
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 long-term inhibition of steps of thyroid hormonogenesis by NO could be of interest in thyroid pathophysiology.