CONICET | Buscador de Institutos y Recursos Humanos

Our group has recently reported that the inhibitory effect of an immune challenge on the reproductive axis activity is mediated by cannabinoid signaling activation through the CB1 receptor, and that its blockade induces a biased pathway to TRPV1 signaling. Since the TRPV1 channel is activated by the endocannabinoid anandamide, in the present study we focused on its role in the control of hypothalamic factors regulating the reproductive axis during an immune challenge. For that purpose, Sprague-Dawley adult male rats (n=6/group) were submitted to an intracerebroventricular administration of a TRPV1 antagonist (Capsazepine, 500ng/5ul) or its vehicle, followed by an intraperitoneal injection of LPS (5mg/kg) or saline 15 min later. Rats were euthanized 3hs post LPS and hypothalamic mRNA expression of proinflammatory cytokines and reproductive neuropeptides were determined by qPCR. Capsazepine by itself increased Il1b and Tnfa mRNA expression, and also enhanced the LPS-inducing effects on Il1b expression. Regarding the hypothalamic reproductive status, Capsazepine and LPS, separately, seemed to switch off the gonadotropin-releasing hormone (GnRH) neuron activity, by decreasing the stimulatory Kisspeptin mRNA (Kiss1), increasing the inhibitory RFamide-related peptide 3 mRNA (Rfrp3), and decreasing Gnrh mRNA. Furthermore, Capsazepine did not modify the inhibitory effects of LPS on Gnrh and Rfrp3, but it prevented the inhibitory effects of LPS on Kiss1. Results suggest that TRPV1 might participate in the maintenance of hypothalamic cytokine basal levels in order to control the reproductive status. The GnRH-controlling neurons responses to TRPV1 blockade during immune challenge could be caused by altered expression of other cannabinoid receptors.