Nitric oxide at the crossroad of immunoneuroendocrine interactions.
Nitric oxide (NO) was initially described as a mediator of endothelial relaxation, and now its participation is recognized in numerous physiological and pathological processes. It was demonstrated that lipopolysaccharide-stimulated corticotropin-releasing factor release involves NO production. Furthermore, it has been shown that interleukin (IL)-1, tumor necrosis factor (TNF)-alpha, IL-6, and IL-2 can stimulate adrenocorticotropic hormone release from anterior pituitary via NO. Also, we found that NO released from hypothalamic NOergic neurons in response to norepinephrine diffuses to luteinizing hormone-releasing hormone (LHRH) neurons that activate cyclooxygenase and guanylate cyclase. This activation results in an increase in prostaglandin E2 and cyclic guanosine monophosphate, respectively, which leads to the exocytosis of LHRH granules. During pathological conditions, such as manganese intoxication, NO production is increased, leading to an increase in LHRH secretion that can advance puberty. In another study we demonstrated that NO reduces oxytocin as well as vasopressin secretion from the posterior pituitary, suggesting it has a modulatory role during dehydration. An increase in NO synthase (NOS) activity and protein in the hippocampus and cerebellum was found in offspring of rats that were subjected to prenatal stress, and this was correlated with behavioral changes in adults. Also NO participates in signal transduction pathways in peripheral tissue in physiological processes, such as in corticosterone release from the adrenal gland. Pathological conditions, such as tumors of the head and neck, that are treated with radiation are followed by xerostomy. In a rat model, radiation diminished NOS activity in the submandibulary gland, and this was followed by inhibition in salivary secretion. In summary, this review describes the wide participation of NO in the cross-talk between neuroendocrine and neuroimmune systems in physiological and pathological processes.
Rettori
Valeria
V
Center of Pharmacological and Botanical Studies, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina.
Fernandez-Solari
Javier
J
Mohn
Claudia
C
Zorrilla Zubilete
María A
MA
de la Cal
Carolina
C
Prestifilippo
Juan Pablo
JP
De Laurentiis
Andrea
A
D000818:Animals; D003345:Corticosterone / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D007107:Immune System / Q000378:metabolism*; D009490:Neurosecretory Systems / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*
D009569:Nitric Oxide; D007987:Gonadotropin-Releasing Hormone; D003345:Corticosterone