Immunocytochemical demonstration of CB1 cannabinoid receptors in the anterior lobe of the pituitary gland.

Both exogenous and endogenous cannabinoids can influence hormone secretion from the anterior pituitary gland. A large body of information proves that the primary target of these effects is the neuroendocrine hypothalamus. However, recent studies using cannabinoid (CB) receptor autoradiography, messenger RNA in-situ hybridization and in-vitro analysis, indicate direct effects of cannabinoids at the level of the anterior pituitary gland itself. In the present paper, the immunocytochemical distribution of CB in the adult rat anterior pituitary was studied using specific polyclonal antibodies against CB1 (central) and CB2 (peripheral) receptors. Due to its resolution, this method allowed identification of individual anterior pituitary cells possessing cannabinoid receptors. The specific hormone immunoreactive cells with receptor-like immunoreactivity were compared on adjacent sections. CB1-like immunoreactivity (CB1ir) was found in the lactotroph cells as well as in luteinizing hormone (LH) secreting gonadotrophs. The CB1ir positive material present in the cytoplasm of these cells was less homogeneous than the hormone immunoreactive material, and it was also seen at the periphery of the cells, presumably on the cell membrane. No CB1ir was found in growth hormone (GH) secreting cells and it was hardly seen in the corticotrophs. No CB1ir was detected in the posterior pituitary. CB2ir was not observed in any part of the pituitary gland. The results support the view that the site of action of cannabinoids on neuroendocrine regulatory mechanisms may be both at pituitary and hypothalamic levels. We suggest that at least the direct effect of cannabinoids on the regulation of LH and prolactin secretion is mediated via CB1 cannabinoid receptors in the anterior pituitary.