The hypothalamo-neurohypophyseal system plays a role in homeostasis under a variety of stress conditions, including endotoxemia. Oxytocin (OXT) and vasopressin (VP) are important hormones synthesized by neurons in the hypothalamic paraventricular and supraoptic nuclei and released into different brain regions and from the neurohypophyseal terminals into the blood in response to many patho-physiological stimuli. However, the mechanism that controls OXT and VP secretion has not been fully elucidated. Nitric oxide (NO) is a known mediator that regulates the release of these hormones. The endocannabinoid system is a new intercellular system that modulates several neuroendocrine actions. Endocannabinoids (eCB) are released as retrograde messengers by many neurons, including hypothalamic magnocellular neurons and cannabinoid receptors are localized within these neurons, as well as in the anterior and posterior pituitary lobes, suggesting an eCB role in the production and release of OXT and VP. Lipopolysaccharide (LPS) injection is a model used as immune challenge. LPS causes a neuroendocrine response that is mediated by cytokines, tumor necrosis factor-α being one of them. We focused on NO and endocannabinoid system participation on OXT and VP production and secretion during basal and stress conditions and found that eCB affect basal OXT and VP secretion by acting differently at each level of the hypothalamo-neurohypophyseal system. After LPS, there is an increase in eCB synthesis that enhances OXT secretion.

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