title: Endogenous thyrocyte-produced nitric oxide inhibits iodide uptake and thyroid-specific gene expression in FRTL-5 thyroid cells.
abstract: 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, Nomega-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, N(g)-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.
authors.affiliation: Centro de Investigaciones en Bioquímica Clínica e Inmunología, Consejo Nacional de Investigaciones Científicas y Técnicas, Departamento de Bioquímica Clínica, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, 5000 Córdoba, Argentina.
authors.forename: Laura
authors.initials: L
authors.lastname: Fozzatti
authors.forename: María L
authors.initials: ML
authors.lastname: Vélez
authors.forename: Ariel M
authors.initials: AM
authors.lastname: Lucero
authors.forename: Juan P
authors.initials: JP
authors.lastname: Nicola
authors.forename: Iván D
authors.initials: ID
authors.lastname: Mascanfroni
authors.forename: Daniela R
authors.initials: DR
authors.lastname: Macció
authors.forename: Claudia G
authors.initials: CG
authors.lastname: Pellizas
authors.forename: Germán A
authors.initials: GA
authors.lastname: Roth
authors.forename: Ana M
authors.initials: AM
authors.lastname: Masini-Repiso
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D002227:Carbazoles / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D015870:Gene Expression; D007211:Indoles / Q000494:pharmacology; D007454:Iodides / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027981:Symporters / Q000235:genetics / Q000378:metabolism; D013954:Thyroglobulin / Q000235:genetics / Q000378:metabolism; D013961:Thyroid Gland / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology; D014162:Transfection / Q000379:methods; D000099209:Sodium-Iodide Symporters
chemical_list: D002227:Carbazoles; D007211:Indoles; D007454:Iodides; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D012333:RNA, Messenger; D027981:Symporters; D013954:Thyroglobulin; D013972:Thyrotropin; D000099209:Sodium-Iodide Symporters; C073601:KT 5823