Participation of the Endocannabinoid System in the Effect of TNF- on Hypothalamic Release of Gonadotropin-Releasing Hormone

Autor:	Stefan R. Bornstein, Valeria Rettori, J Fernández-Solari, Samuel M. McCann, Juan Pablo Prestifilippo
Rok vydání:	2006
Předmět:	Lipopolysaccharides Male AM251 medicine.medical_specialty Cannabinoid receptor medicine.drug_class medicine.medical_treatment Hypothalamus Gonadotropin-releasing hormone Biology General Biochemistry Genetics and Molecular Biology Amidohydrolases Gonadotropin-Releasing Hormone chemistry.chemical_compound Receptor Cannabinoid CB1 History and Philosophy of Science Internal medicine Cannabinoid Receptor Modulators Cyclic AMP medicine Animals Rats Wistar Injections Intraventricular Tumor Necrosis Factor-alpha General Neuroscience Colforsin Anandamide Endocannabinoid system Rats Enzyme Activation Endocrinology chemistry lipids (amino acids peptides and proteins) Cannabinoid Gonadotropin Injections Intraperitoneal Endocannabinoids medicine.drug
Zdroj:	Annals of the New York Academy of Sciences. 1088:238-250
ISSN:	0077-8923
DOI:	10.1196/annals.1366.008
Popis:	It is known that Delta(9)-tetrahydrocannabinol (THC), the major active ingredient of marijuana, can suppress reproductive function. Also, we reported previously that the endocannabinoid, anandamide (AEA), inhibited gonadotropin-releasing hormone (LHRH) release from medial basal hypothalamus (MBH) of male rats incubated in vitro as well as reduced plasma LH levels after i.c.v. AEA injections into the cerebral lateral ventricle. On the other hand, it is known that during endotoxemia the hypothalamic gonadotropin axis is inhibited. Therefore, the aim of the present study was to determine whether the effect of TNF-alpha, a proinflammatory cytokine induced by lipopolysaccharide (LPS) that inhibits LHRH release, is mediated by the activation of the endocannabinoid system. The intraperitoneal injection of LPS (5 mg/kg) as well as the i.c.v. injection of tumor necrosis factor-alpha (TNF-alpha) (100 ng/rat) increased significantly the AEA synthesis measured ex vivo in MBHs removed 3 h after the treatments. To examine the possibility that TNF-alpha also acted by increasing the synthesis of AEA that was released and activated the CB1-r followed by inhibition of LHRH release, we measured the effect of TNF-alpha on the AEA synthase activity in MBHs incubated in vitro. As expected, we found that TNF-alpha (2.9 x 10(-9) M) increased the AEA synthesis. Second, we showed that TNF-alpha reduced significantly the forskolin-stimulated LHRH release and that the CB1-r antagonist AM251 (10(-5) M) blocked that inhibition, supporting the hypothesis that TNF-alpha inhibits LHRH release, acting at least in part by activating the endocannabinoid system. Therefore, our data demonstrate a key role for the endocannabinoid system in the response of the reproductive system to inflammatory signals.
Databáze:	OpenAIRE
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