Localization of an endocannabinoid system in the hypophysial pars tuberalis and pars distalis of man

Abstract

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.

Contributions of endocannabinoid signaling to psychiatric disorders in humans: genetic and biochemical evidence

“…First, endocannabinoid/CB1R signaling regulates the HPA axis response at multiple sites, including the hypothalamus (Di et al, 2003); pituitary (Yasuo et al, 2010) and adrenal gland (Ziegler et al, 2010b). CB1R activation at these sites inhibits HPA axis activation.…”

Impact of Melatonin on Zeitgeber Time-Dependent Changes in Cell Proliferation and Apoptosis in the Adult Murine Hypothalamic-Hypophyseal System

“…These regions hold key functions in neuroendocrine regulation. The PT is the interface between photoperiodically regulated melatonin signaling and neuroendocrine functions and sends signals to the hypothalamus, including the ME, and to the PD via retrograde and anterograde pathways, respectively [13,14]. The ME belongs to the circumventricular organs and is open to the portal vessel system.…”

Endocannabinoids and Kisspeptins: Two Modulators in Fight for the Regulation of GnRH Activity

“…Nevertheless, the localization of CBs in the gonadotropes is confirmed in amphibians and mammals, but not in humans (Cesa et al, 2002;Wenger et al, 1999;Yasuo et al, 2010a). For instance, in rats, AEA exhibits differential effects on the in vitro secretion of LH, and pituitary hormones other than gonadotropins [i.e.…”

“…Recently, ECBs have been included among tuberalins, the messengers supposed to be secreted from the pars tuberalis -a brain area located between the median eminence, the pituitary portal vessels and the pituitary pars distalis -to target the pituitary pars distalis (Yasuo et al, 2010b). In both hamsters and humans, pars tuberalis produces high levels of 2-AG and low levels of other ECBs (AEA, PEA and OEA), while the pituitary pars distalis possesses CB1 (Yasuo et al, 2010a(Yasuo et al, , 2010b. Such a crosstalk might be involved in gonadal response to photoperiodic changes.…”