Identification of Endocannabinoids and Cannabinoid CB₁ Receptor mRNA in the Pituitary Gland

Abstract

Most data on effects of natural and synthetic cannabinoids on anterior pituitary hormone secretion point out to a primary impact on the hypothalamus. There is also some evidence, however, of possible direct actions of these compounds on the anterior pituitary, although the presence of cannabinoid receptors in the pituitary has not been documented as yet. In the present study, we evaluated the presence of cannabinoid CB₁ receptor-mRNA transcripts in the pituitary gland by in situ hybridization. We observed CB₁ receptor-mRNA transcripts in the anterior pituitary and to a lesser extent in the intermediate lobe whereas they were absent in the neural lobe. We then examined whether CB₁ receptor-mRNA levels in both pituitary lobes responded to chronic activation by a specific agonist, as did receptors located in adjacent hypothalamic nuclei and in other brain regions. Daily administration of CP-55,940 for 18 days produced a small, but statistically significant paradoxical increase in CB₁ receptor-mRNA levels in the anterior pituitary, with no changes in the intermediate lobe, in contrast to reduced CB₁ receptor-mRNA levels observed in the ventromedial hypothalamic nucleus (VMN), and to decreased CB₁ receptor binding in the VMN and the arcuate nucleus. The time-course of up-regulation of CB₁ receptor-mRNA transcripts in the anterior lobe was biphasic; daily administration of Δ⁹-tetrahydrocannabinol produced an early and marked decrease in CB₁ receptor-mRNA levels after 1 and 3 days, followed by normalization after 7 days and by a small increase after 14 days. We also checked whether endogenous cannabinoid ligands are present in the anterior pituitary and the hypothalamus. Although anandamide itself was detected only in trace amounts, concentrations of its precursor N-arachidonoyl-phosphatidyl-ethanolamine and of 2-arachidonoyl-glycerol were found in both tissues, suggesting that endocannabinoids may be synthetized in the anterior pituitary. In summary, CB₁ receptors and corresponding ligands seem to be expressed in cells of the anterior and intermediate lobes of the pituitary, but the response of CB₁ receptor-mRNA transcripts in the anterior lobe to chronic agonist activation is different than the desensitization observed in hypothalamic nuclei.

Anti-obesity effect of SR141716, a CB1 receptor antagonist, in diet-induced obese mice

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Influence of intracerebroventricular or intraperitoneal administration of cannabinoid receptor agonist (WIN 55,212-2) and inverse agonist (AM 251) on the regulation of food intake and hypothalamic serotonin levels

“…CB 1 receptors have been detected not only in the hypothalamus (22) , but also in other brain areas involved in the control of food intake, including the nucleus accumbens shell (23) . Recent findings reported by Sano et al (24) demonstrated that D…”

Motivational Effects of Cannabinoids and Opioids on Food Reinforcement Depend on Simultaneous Activation of Cannabinoid and Opioid Systems

“…Consistent with these findings, when we looked at the number of pellets and amount of food consumed per session in the present study, we found a significant increase after THC administration and a significant decrease after rimonabant administration. In addition, high levels of endocannabinoids are present in brain areas involved in the regulation of food intake such the hypothalamus (Gonzalez et al, 1999;Howlett, 2002) and the levels of endocannabinoids are under the control of leptin, a main hormone responsible for negative regulation of food intake (Di Marzo et al, 2001).…”