Evidence for functional CB1 cannabinoid receptor expressed in the rat thyroid.
OBJECTIVE
Previous reports have shown that the Delta(9)-tetrahydrocannabinol (Delta(9)TCH), the major psychoactive cannabinoid components of marijuana, is able [corrected] to inhibit thyroid hormonal activity. The aim of this study was to characterize the CB1 functional expression in the rat thyroid by a multi-methods approach.


RESULTS
RT-PCR was used to detect the mRNA expression of the CB1 cannabinoid receptor (17.8+/-4.0% of the normalizing reference gene beta(2) microglobulin), as well as the expression of the endocannabinoid hydrolyzing enzyme, fatty acid amide hydrolase (46.9+/-4.3% of beta(2) microglobulin), in the rat thyroid gland. The CB1-encoded protein was detected in its glycosylated form (63 kDa) by Western blot, employing a polyclonal antibody, while CB1 immunohistochemical localization showed an intracellular positive staining in both follicular and parafollicular cells. In addition, a 30% decrease in serum levels of both 3,5,3' tri-iodothyronine (T(3)) and thyroxine (T(4)) was detected 4 h after the administration of the synthetic cannabinoid receptor agonist, WIN 55,212-2 (10 mg/kg i.p.). These effects were antagonized by pretreatment with the CB1 antagonist SR 141716A (3 mg/kg i.p.); thyrotrophin levels were unaffected by both treatments.


CONCLUSIONS
These data indicate that functional CB1 receptors which are able to modulate the release of T(3) and T(4) are expressed in the rat thyroid, and suggest a possible role of cannabinoids in the regulation of rat thyroid hormonal activity.
Porcella
Anna
A
CNR Institute of Neurogenetics and Neuropharmacology, Cagliari, Monserrato, Italy. aporcell@unica.it
Marchese
Giorgio
G
Casu
Maria Antonietta
MA
Rocchitta
Antonio
A
Lai
Maria Letizia
ML
Gessa
Gian Luigi
GL
Pani
Luca
L
D000581:Amidohydrolases / Q000235:genetics; D000818:Animals; D048588:Benzoxazines; D015153:Blotting, Western; D063385:Cannabinoid Receptor Modulators; D015870:Gene Expression; D006031:Glycosylation; D007150:Immunohistochemistry; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077285:Rimonabant; D013961:Thyroid Gland / Q000737:chemistry / Q000378:metabolism*; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood; D001613:beta 2-Microglobulin / Q000235:genetics; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D048588:Benzoxazines; D063385:Cannabinoid Receptor Modulators; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D012333:RNA, Messenger; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D000077285:Rimonabant; D013972:Thyrotropin; D013974:Thyroxine; D014284:Triiodothyronine; D001613:beta 2-Microglobulin; D000099252:Fatty Acid Amide Hydrolases; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone