Acute effects of endocannabinoid anandamide and CB1 receptor antagonist, AM251 in the regulation of thyrotropin secretion

Abstract

We examined the acute effects 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, thyroxine (T 4 ), and triiodothyronine (T 3 ) secretions. Euthyroid male rats showed a 42% decrease in serum TSH, 2 h after a single i.p. injection of 0 . 02, but not 0 . 2 mg/kg body weight (BW), anandamide, accompanied by a 39% reduction in serum T 4 , without alteration in serum T 3 . At 0 . 5 and 1 h, these serum hormones showed no significant change. Hypothyroid rats showed a 35% reduction in serum TSH (P!0 . 01), 2 h after anandamide injection, which had no effect on hyperthyroid rats. In both thyroid states, no modification of serum thyroid hormones was observed.Intraperitoneal injection of 0 . 17 or 1 . 7 mg/kg BW AM251 in euthyroid rats caused, 1 . 5 h later, 1 . 7-fold or 4 . 3-fold increase in serum TSH respectively, without changing thyroid hormones. Stimulatory effect of 0 . 17 mg/kg BW AM251 and inhibitory effect of anandamide was abolished in the group injected with AM251 followed by an anandamide injection, 30 min later. Intracerebroventricular injection of 20 ng (but not 200 ng) anandamide induced a decrease in serum TSH at 60 min after injection, which tended to disappear at 120 min. Anterior pituitary explants presented significant reduction in TSH release in the presence of 10 K7 M anandamide in incubation medium, which was blocked by 10 K7 M AM251. In conclusion, anandamide has the ability to acutely inhibit TSH release in eu-and hypothyroid rats, acting at the 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.

Nicotine exposure during breastfeeding alters the expression of endocannabinoid system biomarkers in female but not in male offspring at adulthood

“…32 Studies suggest that endocannabinoids have a negative regulation on TSH, T3 and T4 secretions. 32,61,62 In addition, FAAH knockout mice had significant TSH, T 3 and T 4 reductions. 63 In a previous work, we demonstrated that NIC males showed low TSH, T 3 and T 4 plasma levels, while NIC females had higher T 3 and T 4 .…”

Endocannabinoids in Body Weight Control

“…Administration of AEA led to an acute decrease in TSH and T4, but not T3 levels in rat serum, while application of CB1 inverse agonists acutely raised TSH levels [ 362 ]. These findings are overall in line with previous reports showing that THC reduces serum TSH, T4 and T3 [ 363 ], while the synthetic CB1/CB2 agonist WIN 55212-2 reduced T4 and T3, but did not alter TSH levels [ 364 ].…”

Endocannabinoids and the Endocrine System in Health and Disease

“…It is interesting in this regard that glucocorticoid-induced mobilization of ECS has been shown to inhibit glutamate release onto TRH-positive neurons in the hypothalamus (Di et al, 2003), suggesting that eCBs link stress and suppression of the HPT axis. Cannabinoids have also been shown to suppress the HPT axis at the pituitary (Veiga et al, 2008) and thyroid gland (Porcella et al, 2002). However, inhibition at the first step in a cascade such as the HPT axis will have the greatest impact in vivo .…”