Normal human pituitary gland and pituitary adenomas express cannabinoid receptor type 1 and synthesize endogenous cannabinoids: first evidence for a direct role of cannabinoids on hormone modulation at the human pituitary level.
The Journal of Clinical Endocrinology & Metabolism. 2001-06-01; 86(6): 2687-2696
DOI: 10.1210/jcem.86.6.7565
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1. J Clin Endocrinol Metab. 2001 Jun;86(6):2687-96.
Normal human pituitary gland and pituitary adenomas express cannabinoid receptor
type 1 and synthesize endogenous cannabinoids: first evidence for a direct role
of cannabinoids on hormone modulation at the human pituitary level.
Pagotto U(1), Marsicano G, Fezza F, Theodoropoulou M, Grübler Y, Stalla J,
Arzberger T, Milone A, Losa M, Di Marzo V, Lutz B, Stalla GK.
Author information:
(1)Neuroendocrinology Group, Max Planck Institute of Psychiatry, 80804 Munich,
Germany.
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.
DOI: 10.1210/jcem.86.6.7565
PMID: 11397872 [Indexed for MEDLINE]