Localization of an endocannabinoid system in the hypophysial pars tuberalis and pars distalis of man.
The hypophysial pars tuberalis (PT) acts as an important interface between neuroendocrine brain centers (hypothalamus, pineal organ) and the pars distalis (PD) of the hypophysis. Recently, we have identified an endocannabinoid system in the PT of hamsters and provided evidence that 2-arachidonoylglycerol is a messenger molecule that appears to play an essential role in seasonal reproduction and prolactin release by acting on the cannabinoid receptors in the PD. We now demonstrate the enzymes involved in endocannabinoid synthesis and degradation, namely sn-1-selective diacylglycerol lipase α, N-acylphosphatidylethanolamine-specific phospholipase D, and monoacylglycerol lipase, in the PT of man by means of immunohistochemistry. High-performance liquid chromatography coupled with tandem mass spectrometry revealed 2-arachidonoylglycerol and other endocannabinoids in the human PT. Furthermore, we detected the expression of the cannabinoid receptor 1 (CB1), a primary receptor for endocannabinoids, in the PD. Double-immunofluorescence staining for CB1 and various hypophysial hormones or S-100, a marker for folliculostellate (FS) cells, revealed that CB1 immunoreactivity was mainly localized to corticotrophs and FS-cells. A limited number of lactotrophs and somatotrophs also showed CB1 immunoreactivity, which was however absent from gonadotrophs and thyrotrophs. Our data thus indicate that the human PT comprises an endocannabinoid system, and that corticotrophs and FS-cells are the main target cells for endocannabinoids. The functional significance of this newly discovered pathway remains to be elucidated in man; it might be related to the control of stress responses and/or reflect a remnant seasonal control of hypophysial hormonal secretion.
Dr. Senckenbergische Anatomie, Institut für Anatomie II, Goethe-Universität Frankfurt am Main, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany.
Shinobu
S
Yasuo
Claudia
C
Unfried
Mattias
M
Kettner
Gerd
G
Geisslinger
Horst-Werner
HW
Korf
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001095:Arachidonic Acids / Q000032:analysis / Q000378:metabolism*; D063385:Cannabinoid Receptor Modulators / Q000032:analysis / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D063388:Endocannabinoids; D005260:Female; D005989:Glycerides / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D018377:Neurotransmitter Agents / Q000032:analysis / Q000378:metabolism*; D010903:Pituitary Gland, Anterior / Q000737:chemistry / Q000201:enzymology*; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D005989:Glycerides; D018377:Neurotransmitter Agents; D043884:Receptor, Cannabinoid, CB1; C094503:glyceryl 2-arachidonate