INVESTIGADORES
PELLIZAS Claudia Gabriela
artículos
Título:
Inhibition of iodide uptake and thyroid specific genes mRNA expresión by nitric oxide/guanylate cyclase pathway in FRTL-5 cells
Autor/es:
BAZZARA LG; COSTAMAGNA ME; CABANILLAS AM; VÉLEZ ML; FOZZATTI L; PELLIZAS CG; MASINI-REPISO AM
Revista:
THYROID
Editorial:
mary Ann Liebert
Referencias:
Lugar: New York; Año: 2007 vol. 17 p. 117 - 118
ISSN:
1050-7256
Resumen:
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. Design: Cells were treated with the NO donor sodium nitroprusside (SNP)
for 2472 h. Main Outcome: SNP (50500 mmol=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
0
,5
0
-cyclic guanosine monophosphate (cGMP) production. 3
0
,5
0
-cyclic adenosine phosphate (cAMP)
generation was reduced by a high SNP concentration after 48 h. 8-Bromoguanosine 3
0
,5
0
-cyclic monophosphate
(8-Br-cGMP), a cGMP analog, inhibited iodide uptake as well as TPO and TG mRNA expression. The cGMPdependent protein kinase (cGK) inhibitor KT-5823 reversed SNP or 8-Br-cGMP-inhibited iodide uptake. Thyroidstimulating hormone pretreatment for 2448 h prevented SNP-reduced iodide uptake although nitrite levels
remained unaffected. Conclusion: 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