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


METHODS
Cells were treated with the NO donor sodium nitroprusside (SNP) for 24-72 h.


RESULTS
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.


CONCLUSIONS
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.
Bazzara
Leonardo Gabriel
LG
Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, Ciudad Universitaria, Córdoba, Argentina.
Vélez
María Laura
ML
Costamagna
María Eugenia
ME
Cabanillas
Ana María
AM
Fozzatti
Laura
L
Lucero
Ariel Maximiliano
AM
Pellizas
Claudia Gabriela
CG
Masini-Repiso
Ana María
AM
D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D007453:Iodide Peroxidase / Q000235:genetics*; D007454:Iodides / Q000493:pharmacokinetics*; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013954:Thyroglobulin / Q000235:genetics*; D013961:Thyroid Gland / Q000166:cytology / Q000378:metabolism*; D013963:Thyroid Hormones / Q000096:biosynthesis; D013972:Thyrotropin / Q000378:metabolism* / Q000494:pharmacology
D002227:Carbazoles; D007454:Iodides; D020030:Nitric Oxide Donors; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D013963:Thyroid Hormones; C073601:KT 5823; D009599:Nitroprusside; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D013972:Thyrotropin; D013954:Thyroglobulin; D000242:Cyclic AMP; D007453:Iodide Peroxidase; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP