Manganese increases LHRH release through NO and cGMP

PRESTIFILIPPO JP; FERNÁDEZ-SOLARI J; MOHN C; DE LAURENTIIS A; MCCANN SM; DEES WL; RETTORI V

Buenos Aires

Congreso; XXII Latin-American and First Ibero-American Congress of Physiological Sciences; 2006

SAFIS y ALACF

Manganese (Mn) is an essential metal but in high doses has a toxic action in the brain resulting in a neurological disorder similar to Parkinson’s disease. Mn increased plasma levels of  luteinizing hormone (LH) when injected into the third cerebral ventricle in prepuberal rats. On the other hand, nitric oxide (NO) plays a crucial role on reproduction, principally by the activation of luteinizing hormone-releasing hormone (LHRH) release from the hypothalamus and the subsequent release of LH by gonadotropes from the pituitary gland. Therefore, the aim of the present work was: to determine the effect of Mn on LHRH release and NO production in the medial basal hypothalamus (MBH) of adult Sprague Dawley male rats (250g). After decapitation and removal of the brain, the MBH was dissected and incubated in a static incubation system in Krebs-Ringer buffer. Groups (n:6-8 MBH) were pre-incubated individually for 15 min and then incubated for another 30 min with different drugs:1)Control (Krebs); 2)Mn (500µM); 3)L-NAME (10-3M), an inhibitor of NOS activity; 4)Hemoglobin (Hb 40ug/ml), a scavenger of NO; 5)Methylene Blue (MB, 10.10-3M), an inhibitor of guanylyl cyclases; 6)Mn+L-NAME; 7)Mn+Hemoglobin; 8)Mn+Methylene Blue. cGMP in the tissue and LHRH in the media were measured by RIA and NOS activity by the technique of 14C-arginine. All data are expressed as means+SEM. Comparisons between groups were performed by using ANOVA followed by the Newman-Keuls test. Differences with p < 0.05 were considered significant. Mn increased LHRH release (p<0.001), NOS activity (p<0.01) and cGMP content (p<0.01). L-NAME blocked the stimulatory effect of Mn on LHRH release (p<0.01) and the increase of cGMP (p<0.05). Hb completely blocked the stimulatory effect of Mn on LHRH release (p<0.001). MB blocked the Mn-stimulated LHRH release (p<0.01) and the increase on cGMP content (p<0.01). These results indicate that NO and cGMP mediate the Mn-stimulated LHRH release in the hypothalamus. (BID  1728 OC-AR PICT 14264; PIP 6149)