HYPOTHALAMIC CB1 RECEPTOR ACTIVATION INHIBITS THE INFLAMMATORY RESPONSE INDUCED BY ENDOTOXIC STRESS IN DETRIMENTAL OF THE REPRODUCTIVE FUNCTION.

SURKIN PABLO NICOLÁS; ASTRAUSKAS JULIA IRENE; FERNANDEZ SOLARI JAVIER ; DI ROSSO MARIA EMILIA; DE LAURENTIIS ANDREA; GALLINO SOFIA LUDMILA ; GENARO ANA MARIA

MAR DEL PLATA

Congreso; LXI REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC); 2016

SAIC, SAI, SAFE

It is known that endotoxic stress (ES) inhibits reproductive function,and that endocannabinoids (EC) modulate sexual hormones.We hypothesize that ES inhibits reproductive axis via EC system.Thus, the objective of this study was to evaluate the participation ofthe hypothamic cannabinoid receptor CB1 (CB1R) on hypothalamic-pituitary-gonadal axis in rats submitted to ES. Sprague Dawleyrats (n=6/group) were implanted with intracerebroventricular (icv)cannulas at the cerebral lateral ventricle by stereotaxis. 6 daysafter surgery a silastic catheter was introduced in the right jugularvein. The next day, rats were treated via icv with CB1R antagonist,(AM251, 500ng/5ul) or saline, followed by an intraperitoneal (ip)injection of LPS (5mg/kg) or saline 15 min later. Blood sampleswere obtained at -30, 30, 60, 90 and 180min from LPS injection.Plasma TNFα by ELISA and LH by RIA were determined. In otherexperiment, rats equally treated were euthanized 90 or 180minpost LPS injection and medial basal hypothalamus (MBH) andadenohypophysis (AH) removed. The tissues from 90 min treatedrats were used for qPCR of IL1β, TNFα, TRPV, CB1R, and GnIH(the last only in MBH). Ex vivo experiments were performed with180min explants to measure GnRH (in MBH) by RIA and TNFα(in MBH and AH) by ELISA in media. Results: Plasma TNFαincreased and LH decreased in LPS treated rats (p