Inhibition of the release of Gonadotropin Releasing Hormone (LH-RH) by pro-inflammatory cytokines.

BESUHLI DE RETTORI V; J. FERNÁNDEZ-SOLARI; DE LAURENTIIS A; S.M. MCCANN

Madrid

Simposio; 2nd Iberoamerican Congress on Neuroimmunomodulation; 2007

It is known that endotoxemia can suppress reproductive function. Also, we reported that IL-1a inhibited norepinephrine stimulated LH-RH release from medial basal hypothalamus (MBH) of rats and reduced plasma LH after injections into cerebral lateral ventricle (icv). Similar results were also seen with TNFa. Furthermore, intraperitoneal (i.p.) injection of LPS induced IL-1b mRNA in several brain areas and increased the number of IL-1a immunostained neurons in hypothalamus. Since the endocannabinoid system elicit similar inhibitory effect on LH-RH release and CB1 receptors were found colocalized on hypothalamic TH neurons, we studied if there was a link between the two systems. The ip injection of LPS (5mg/Kg) as well as the icv injection of TNFa (100 ng/rat) increased significantly the anandamide (AEA) synthesis measured ex vivo in MBH´s 3 h after the treatments. Also we found that TNFa (2.9x10-9M) increased the AEA synthase activity in MBH´s in vitro. Furthermore, TNFa reduced the forskolin-stimulated LHRH release and the CB1-receptor antagonist, AM251 (10-5M), blocked this inhibition. We concluded that the inhibition of LH-RH release by TNFa is mediated by the activation of the endocannabinoid system. Therefore, our data demonstrate a key role for the endocannabinoid system in the inhibition of reproduction during endotoxemia. (BID 1728-OC/AR PICT 03-14264)