Little is known about the expression and function of
cannabinoid receptor type 1 (CB1) in the human pituitary gland. The aim of this study was to investigate CB1 expression in human normal and tumoral pituitaries by in situ hybridization and immunohistochemistry using an antibody against CB1. CB1 was found in corticotrophs, mammotrophs, somatotrophs, and folliculostellate cells in the anterior lobe of normal pituitary. After examination of 42
pituitary adenomas, CB1 was detected in
acromegaly-associated
pituitary adenomas, Cushing's
adenomas, and
prolactinomas, whereas faint or no expression was found in nonfunctioning
pituitary adenomas. Experiments with cultured
pituitary adenoma cells showed that the CB1 agonist
WIN 55,212--2 inhibited GH secretion in most of
acromegaly-associated
pituitary adenomas tested and that the CB1 antagonist
SR 141716A was generally able to reverse this effect. Moreover,
WIN 55,212--2 was able to suppress GHRH-stimulated GH release, and this effect was not blocked by coincubation with
SR 141716A, possibly indicating a non-CB1-mediated effect. In contrast,
WIN 55,212--2 was ineffective on GH-releasing
peptide-stimulated GH release. In four Cushing's
adenomas tested,
WIN 55,212--2 was not able to modify basal
ACTH secretion. However, simultaneous application of CRF and
WIN 55,212--2 resulted in a synergistic effect on
ACTH secretion, and this effect could be abolished by
SR 141716A, demonstrating a CB1-mediated effect. In the single case of
prolactinomas tested,
WIN 55,212--2 was able to inhibit basal secretion of PRL. Finally, the presence of
endocannabinoids (
anandamide and 2-arachidonoylglycerol) was investigated in normal and tumoral pituitaries. All tumoral samples had higher contents of
anandamide and
2-arachidonoylglycerol compared with the normal hypophysis. Moreover,
endocannabinoid content in the different
pituitary adenomas correlated with the presence of CB1, being elevated in the tumoral samples positive for CB1 and lower in the samples in which no or low levels of CB1 were found. The results of this study point to a direct role of
cannabinoids in the regulation of human pituitary
hormone secretion.