Recent evidence suggests that the gases nitric oxide and carbon monoxide are produced in the brain and function as neurotransmitters. This brief review focuses on the role of nitric oxide and carbon monoxide as transmitters and biologic mediators in neuroendocrine-immune interactions. Evidence suggests that nitric oxide is an important component of the accelerator mechanism in the hypothalamus, which controls gonadotropin-releasing hormone (GnRH) secretion and the preovulatory luteinizing hormone surge. The facilitatory effect of nitric oxide on GnRH secretion appears to be due to its ability to modulate the heme-containing enzyme, guanylate cyclase, leading to enhanced production of the second-messenger molecule, cyclic GMP. Carbon monoxide may also play a role in stimulating GnRH secretion as heme molecules stimulate GnRH release in vitro, an effect that requires heme oxygenase activity and is blocked by the gaseous scavenger molecule, hemoglobin. In contrast to its stimulatory effects on GnRH and luteinizing hormone secretion, nitric oxide appears to function to restrain the hypothalamic-pituitary-adrenal (HPA) axis, because it inhibits HPA stimulation by various stimulants such as interleukin-1 β, vasopressin, and inflammation. The inhibition of the HPA axis by nitric oxide during inflammation would fit a proinflammatory role of nitric oxide because it would suppress the release of the anti-inflammatory corticosteroids from the adrenal. Carbon monoxide also suppresses stimulated corticotropin-releasing hormone release and may also function to restrain the HPA axis. Taken as a whole, the available data suggest that the diffusible gases nitric oxide and carbon monoxide act as novel transmitters in the hypothalamus to modulate neuroendocrine-immune function and interactions.
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism