INVOLVEMENT OF THE cGMP PATHWAY IN THE INHIBITION OF THE IODIDE UPTAKE AND THE EXPRESSION OF THYROID SPECIFIC GENES IN FRTL-5

BAZZARA LEONARDO GABRIEL; COSTAMAGNA MARIA EUGENIA; CABANILLAS ANA MARIA; VÉLEZ MARIA LAURA; FOZZATTI LAURA; MASINI-REPISO ANA MARIA

RIO DE JANEIRO

Congreso; IX Congreso de la Sociedad Latinoamericana de Tiroides (SLAT); 2001

Sociedad Latinoamericana de Tiroides (SLAT)

Previous reports indicated that nitric oxide (NO) inhibits the iodide uptake in several species and the thyroperoxidase (TPO) mRNA expression in FRTL-5 cells. This work was aimed to analyse the role of the guanylyl cyclase/cyclic GMP (cGMP) pathway in the inhibitory effect of NO on iodide uptake and in the expression of TPO and thyroglobulin (TG) mRNA in TSH (500uIU/ml)-stimulated FRTL-5. Sodium Nitroprusside (SNP), a NO donor), increased cGMP levels (RIA) in a concentration and time-dependent manner. The cAMP level (RIA) decreased after 48 h of incubation with 500 uM SNP and was not modified at shorter times and lower SNP concentrations. An increase of cGMP was induced by TSH. The inhibition exerted by SNP or 8-Br-cGMP for 24 h on the iodide uptake (131I) was reversed bt KT-5823 (1-10 uM) an inhibitor of the cGMP-dependent protein kinase (PKG). The TPO and TG mRNA expression (Northern-blot) was significantly reduced by 8-Br-cGMP. In conclusion, an activation of PKG seems to be involved in the NO/cGMP-induced inhibition of iodide uptake in FRTL-5. A reduction in the cAMP production could be relevant in the action of high NO/cGMP levels. Evidence is provided for a role of the cGMP pathway in the regulation of thyroid specific genes.