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Accepted Preprint first posted online on 28 August 2008

Journal of Endocrinology 2008;199:235.

Journal of Endocrinology (2008) In press
DOI: 10.1677/JOE-08-0380
© 2008 Society for Endocrinology
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RESEARCH

Acute Effects of Endocannabinoid Anandamide and CB-1 receptor antagonist, AM251 in the Regulation of Thyrotropin Secretion

Malc Veiga, Flavia Bloise, Rh Costa-e-Sousa, Luana Souza, Norma Almeida, Kj Oliveira and Carmen Pazos-Moura

M Veiga, Instituto de Biofisica Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
F Bloise, Instituto de Biofisica Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
R Costa-e-Sousa, Instituto de Biofisica Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
L Souza, Instituto de Biofisica Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
N Almeida, Instituto de Biofisica Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
K Oliveira, Instituto de Biofisica Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
C Pazos-Moura, Instituto de Biofisica Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

Correspondence: Carmen Pazos-Moura, Email: cpazosm{at}pq.cnpq.br

Abstract

We examined the acute effect of endocannabinoid, anandamide, and of synthetic cannabinoid receptor antagonist, AM251[N-(piperidin-1-yl)-1-(2,4-dichlorophenyl)-5-(4-chlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide], on TSH, thyroxin (T4) and triiodothyronine (T3) secretion. Euthyroid male rats showed 42% decrease in serum TSH, two hours after a single intra-peritoneal injection of 0.02, but not 0.2mg/kg BW, anandamide, accompanied by 39% reduction in serum T4, without alteration in serum T3. At 0.5 and 1 hour, these serum hormones showed no significant change. Hypothyroid rats showed 35% reduction in serum TSH (P<0.01), 2 hours after anandamide injection, which had no effect on hyperthyroid rats. In both thyroid states no modification of serum thyroid hormones was observed. Intra-peritoneal injection of 0.17 or 1.7 mg/kgBW AM251 in euthyroid rats caused, 1.5 h latter, 1.7-fold or 4.3-fold increase in serum TSH, respectively, without changing thyroid hormones. Stimulatory effect of 0.17 mg/kgBW AM251 and inhibitory effect of anandamide was abolished in the group injected with AM251 followed by anandamide injection, 30 minutes latter. Intracerebroventricular injection of 20ng (but not 200ng) anandamide induced a decrease in serum TSH at 60 minutes after injection, which tended to disappear at 120 min. Anterior pituitaries explants presented significant reduction in TSH release in the presence of 10-7M anandamide in incubation medium, which was blocked by 10-7M AM251. In conclusion, anandamide has the ability to acutely inhibit TSH release in eu- and hypothyroid rats, acting at hypothalamus-pituitary axis. Since, in addition, the cannabinoid receptor antagonist, AM251 increased TSH release, we suggest that endocannabinoid system has a role as negative regulator of TSH secretion.







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