Endogenous thyrocyte-produced nitric oxide inhibits iodide uptake and thyroid-specific gene expression in FRTL-5 thyroid cells

• Published in: Journal of endocrinology Vol. 192; no. 3; pp. 627 - 637
• Main Authors: Fozzatti, Laura, Vélez, María L, Lucero, Ariel M, Nicola, Juan P, Mascanfroni, Iván D, Macció, Daniela R, Pellizas, Claudia G, Roth, Germán A, Masini-Repiso, Ana M
• Format: Journal Article
• Language: English
• Published: Colchester BioScientifica 01.03.2007; Portland Press
• Subjects: Animals; Biological and medical sciences; Blotting, Northern; Carbazoles - pharmacology; Cell Line; Cell Proliferation - drug effects; Fundamental and applied biological sciences. Psychology; Gene Expression; Hormones. Regulation; Indoles - pharmacology; Iodides - metabolism; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide - analysis; Nitric Oxide - metabolism; Nitric Oxide Synthase - antagonists & inhibitors; Promoter Regions, Genetic; Rats; Regular papers; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Symporters - genetics; Symporters - metabolism; Thyroglobulin - genetics; Thyroglobulin - metabolism; Thyroid Gland - metabolism; Thyroid. Parathyroid. Ultimobranchial body; Thyrotropin - pharmacology; Transfection - methods; Vertebrates: endocrinology; Endocrine gland; Iodides; Rat; Rodentia; Thyroid gland; Gene expression; In vitro; Uptake; Vertebrata; Mammalia; Cell line; Nitric oxide; Hormonal regulation; Biological effect
• ISSN: 0022-0795; 1479-6805
• DOI: 10.1677/joe.1.06967

Nitric oxide (NO) is a free radical that mediates a wide array of cell functions. It is generated from l-arginine by NO-synthase (NOS). Expression of NOS isoforms has been demonstrated in thyroid cells. Previous reports indicated that NO donors induce dedifferentiation in thyrocytes. However, the functional significance of endogenous thyrocyte-produced NO has not been explored. This work aimed to study the influence of endogenous NO on parameters of thyroid cell function and differentiation in FRTL-5 cells. We observed that treatment with the NOS inhibitor, Nω-nitro-l-arginine methyl ester (l-NAME), increased the TSH-stimulated iodide uptake. The TSH-induced sodium iodide symporter (NIS) and thyroglobulin (TG) mRNA expressions were increased after incubation with l-NAME. In transient transfection assays, TSH-stimulated transcriptional activities of NIS and TG promoters were increased by l-NAME. An increment of the TSH-stimulated cell proliferation was observed after NOS inhibition. Similar results were obtained when the action of another NOS inhibitor, Ng-monomethyl-l-arginine, was analysed for most of these studies. The production of NO, which was not detectable in basal conditions, was increased by TSH. Our data provide strong evidence that endogenous NO could act as a negative signal for TSH-stimulated iodide uptake and thyroid-specific gene expression as well as proliferation in thyrocytes. These findings reveal a possible new inhibitory pathway in the regulation of thyroid cell function.