In vitro effect of delta 9-tetrahydrocannabinol to stimulate somatostatin release and block that of luteinizing hormone-releasing hormone by suppression of the release of prostaglandin E2.

RETTORI, VALERIA; AGUILA MC; GIMENO MARTA; FRANCHI, ANA MARIA; MCCANN SAMUEL

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

NATL ACAD SCIENCES

Lugar: Washington DC, USA; Año: 1990 vol. 87 p. 10063 - 10066

0027-8424

Previous in vivo studies have shown thatA9-tetrahydrocannabinol (THC), the principal active ingredientin marijuana, can suppress both luteinizing hormone (LH)and growth hormone (GH) secretion after its injection into thethird ventricle of conscious male rats. The present studies weredesigned to determine the mechanism of these effects. Variousdoses of THC were incubated with either stalk median eminencefragments (MEs) or mediobasal hypothalamic (MBH)fragments in vitro. Although THC (10 nM) did not alter basalrelease of LH-releasing hormone (LHRH) from MEs in vitro, itcompletely blocked the stimulatory action of dopamine ornorepinephrine on LHRH release. The effective doses to blockLHRH release were associated with a blockade of synthesis andrelease of prostaglandin E2 (PGE2) from MBH in vitro. Incontrast to the suppressive effect of THC on LHRH release,somatostatin release from MEs was enhanced in a dose-relatedmanner with a minimal effective dose of 1 nM. Since PGE2suppresses somatostatin release, this enhancement may also berelated to the suppressive effect ofTHC on PGE2 synthesis andrelease. We speculate that these actions are mediated by therecently discovered THC receptors in the tissue. The resultsindicate that the suppressive effect of THC on LH release ismediated by a blockade of LHRH release, whereas the suppressiveeffect of the compound on growth hormone release ismediated, at least in part, by a stimulation of somatostatinrelease.