GASEOUS TRANSMITTERS AND NEUROENDOCRINE REGULATION

Recent work has demonstrated that the brain has the capacity to synthe size impressive amounts of the gases nitric oxide (NO) and carbon mono xide (GO). There is growing evidence that these gaseous molecules func tion as novel neural messengers in the brain. This article reviews the pertinent literature concerning the putative role of NO and CO as cri tical neurotransmitters and biological mediators of the neuroendocrine axis. Abundant evidence is presented which suggests that NO has an im portant role in the control of reproduction due to its ability to cont rol GnRH secretion from the hypothalamus. NO potently stimulates GnRH secretion and also appears to mediate the action of one of the major t ransmitters controlling GnRH secretion, glutamate. Evidence is present ed which suggests that NO stimulates GnRH release due to its ability t o modulate the heme-containing enzyme, guanylate cyclase, which leads to enhanced production of the second messenger molecule, cGMP. A physi ological role for NO in the preovulatory LH surge was also evidenced b y findings that inhibitors and antisense oligonucleotides to nitric ox ide synthase (NOS) attenuate the steroid-induced and preovulatory LH s urge. CO may also play a role in stimulating GnRH secretion as heme mo lecules stimulate GnRH release in vitro, an effect which requires heme oxygenase activity and is blocked by the gaseous scavenger molecule, hemoglobin. Evidence is also reviewed which suggests that NO acts to r est rain the hypothalamic-pituitary-adrenal (HPA) axis, as it inhibits HPA stimulation by various stimulants such as interleukin-1 beta, vas opressin, and inflammation. This effect fits a proinflammatory role of NO as it leads to suppression of the release of the anti-inflammatory corticosteroids from the adrenal. Although not as intensely studied a s NO, CO has been shown to suppress stimulated CRH release and may als o function to restrain the HPA axis. Evidence implicating NO in the co ntrol of prolactin and growth hormone secretion is also reviewed and d iscussed, as is the possible role of NO acting directly at the anterio r pituitary. Taken as a whole, the current data suggest that the diffu sible gases, NO and CO, act as novel transmitters in the neuroendocrin e axis and mediate a variety of important neuroendocrine functions.