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

FOZZATTI LAURA; VÉLEZ MARÍA L.; LUCERO ARIEL M.; NICOLA JUAN P.; MASCANFRONI IVÁN D.; MACCIÓ DANIELA R.; PELLIZAS CLAUDIA G.; ROTH GERMAN A.; MASINI-REPISO ANA M.

JOURNAL OF ENDOCRINOLOGY

Society for Endoccrinology

Lugar: Great Britain; Año: 2007 vol. 192 p. 627 - 637

0022-0795

Endogenous thyrocyte-produced nitric oxide inhibits iodide uptake and thyroid-specific gene expression in FRTL-5 thyroid cells. Fozzatti L, Velez ML, Lucero AM, Nicola JP, Mascanfroni ID, Maccio DR, Pellizas CG, Roth GA, Masini-Repiso AM. Centro de Investigaciones en Bioquimica Clinica e Inmunologia, Consejo Nacional de Investigaciones Cientificas y Tecnicas, Departamento de Bioquimica Clinica, Universidad Nacional de Cordoba, Haya de la Torre y Medina Allende, 5000 Cordoba, Argentina. 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.