The Endocannabinoid, Anandamide, Increases Plasma PRL and LH

SCORTICATI, C; MOHN, C; VISSIO, P; LOMNICZI, A; DE LAURENTIIS, A; SEILICOVICH, A; MCCANN, S; RETTORI, V

San Diego, USA

Congreso; Endo 2002 84RD Annual Metting of The Endocrine Society; 2002

Endocrine Society

Anandamide (AEA), an arachidonic acid derivative (arachidonyl ethanolamide),is an endogenous ligand of cannabinoid receptors (CBl) found in brain, includinghypothalamus. Previously we have reported that the third ventricular (3V) injection of AEA to adult male rats lowered plasma PRL and LH, and increased DA content and the DOPAC/DA ratio in medial basal hypothalamus (MBH). Since it has been shown that estrogen can reverse the inhibitory action of progesterone and certain peptides, we studied the effect of AEA on plasma PRLand LH levels, DA content and activity in hypothalami of conscious, freely moving, ovariectomized, estrogen-primed adult rats bearing implanted 3V cannulae and external jugular catheters. AEA (2Ong/2ul) or AM251(CB 1 antagonist) (200ng/2ul) + AEA or vehicle (2ul) were microinjected into the 3V and blood samples (0.5 mI) removed every 30 minutes for 150 min to determine the effect on plasma PRL and LH. There was a significant increase (P<O.OI) in the areas under the curves of plasma PRL and LH in AEA-injected rats. AM25l had no effect itself but antagonized significantly (p<O.05) these effects of AEA. DA content in the MBH did not change, but there was significantly (p<O.05) lower DA activity as shown by a decrease in DOPAC/DA ratio. Immunocytochemical studies using a double immunofluorescent staining technique, visualized a partial co-localization of tyrosine hydroxylase and CB 1 receptors in the periventricular and arcuate hipothalamic nuclei. The present results demonstrate that anandamidestimulates PRL and LH secretion by acting on its specific CB 1 receptors, since these actions were blocked by a specific antagonist. These effects are completely opposite in direction from the ones that were observed in adult male rats, where a highly significant inhibitory action on PRL and LH secretion was observed. In AEA-injected rats the DA activity was decreased in ovariectomized, estrogen-primed animals in contrast to the highly significant increase observed in male rats. The results suggest that in the estrogen-primed rats dopaminergic inhibitory control of PRL and LHRH is reversed resulting in increased plasma PRL and LH in ABA-injecte