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

DI ROSSO, MARIA EMILIA; SURKIN, PABLO NICOLAS; DE LAURENTIIS, ANDREA; ASTRAUSKAS, JULIA IRENE ; FERNÁNDEZ-SOLARI, JAVIER ; GALLINO, SOFIA LUDMILA; GENARO, ANA MARIA

Mar del Plata

Congreso; LXI Reunión Científica de la Sociedad Argentina de Investigación Clínica (SAIC); LXIV Reunión Anual de la Sociedad Argentina de Inmunología (SAI) y XLVIII Reunión Anual de la Sociedad Argentina de Farmacología Experimental (SAFE); 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 of the hypothamic cannabinoid receptor CB1 (CB1R) on hypothalamic-pituitary-gonadal axis in rats submitted to ES. Sprague Dawley rats (n=6/group) were implanted with intracerebroventricular (icv) cannulas at the cerebral lateral ventricle by stereotaxis. 6 days after surgery a silastic catheter was introduced in the right jugular vein. 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 samples were obtained at -30, 30, 60, 90 and 180min from LPS injection.Plasma TNFα by ELISA and LH by RIA were determined. In other experiment, rats equally treated were euthanized 90 or 180min post LPS injection and medial basal hypothalamus (MBH) and adenohypophysis (AH) removed. The tissues from 90 min treated rats were used for qPCR of IL1β, TNFα, TRPV, CB1R, and GnIH (the last only in MBH). Ex vivo experiments were performed with 180min explants to measure GnRH (in MBH) by RIA and TNFα (in MBH and AH) by ELISA in media. Results: Plasma TNFβ increased and LH decreased in LPS treated rats (p