Role of nitric oxide in the control of luteinizing hormone-releasing hormone release in vivo and in vitro.

Abstract

Nitric oxide (NO) synthase, the enzyme which converts arginine into citrulline plus NO, a highly active free radical, has been found in many neurons in the brain, including neurons in the hypothalamus. Our previous experiments showed that norepinephrine-induced prostaglandin E2 release from hypothalamic explants incubated in vitro is mediated by NO. Since the release of luteinizing hormone-releasing hormone (LHRH) is also driven by norepinephrine and prostaglandin E2, we hypothesized that NO might also control pulsatile release of LHRH in vivo, resulting in turn in pulsatile release of luteinizing hormone (LH). To ascertain the role of NO in control of pulsatile LH release in vivo, an inhibitor of NO synthase, NG_monomethyl-L-arginine (NMMA), was microinjected into the third cerebral ventricle (1 mg/5 pi) of conscious castrate male rats at time 0 and 60 min later; blood samples were taken every 10 min during this period. NMMA blocked pulsatile LH release within 20 min, and plasma LH concentration declined further without pulses after the ij'ection at 60 min. Pulsatile release of LH was not altered in diluent-injected controls. NMMA did not alter pulsatile release of follidestimulating hormone, which suggests that its release does not require NO. Incubation of medial basal hypothalami with norepinephrine (10 pM) ind.uced an increase in LHRH release that was inhibited by NMMA (300 PM). NMMA alone did not alter basal LHRH release, whereas it was augmented by sodium nitroprusside (100 FM), which releases NO spontaneously. This augmentation was prevented by hemoglobin (2 jug/ml), which binds the NO released by nitroprusside. Our previous experiments showed that norepinephrine-induced release of prostaglandin E2 is mediated by NO. Nitric oxidergic neurons were visualized in the median eminence adjacent to the LHRH terminals. The combined in vivo and in vitro results indicate that the pulsatile release of LHRH induced by norepinephrine is brought about by al-adrenergic activation of NO synthase.NO then induces prostaglandin E2 release that activates exocytosis of LHRH secretory granules into the portal vessels to induce pulsatile LH release.Nitric oxide (NO) released from vascular endothelium by cholinergic stimulation diffuses to the adjacent vascular smooth muscle and elicits relaxation (1-4). The mechanism by which this occurs begins with the release of acetylcholine from cholinergic terminals. It combines with muscarinic cholinergic receptors on the endothelial cells and increases intracellular Ca2+. The Ca2+ interacts with calmodulin to activate constitutive NO synthase, which then converts arginine into NO plus citrulline (1-4). Constitutive NO synthase occurs in the brain (5, 6); this enzyme has been purified and antibodies have been generated against it (7,8). NeuronsThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.containing the constitutive NO ...

Role of leptin in hypothalamic–pituitary function

“…Since, NPY inhibited LH release in intact and castrated male and ovariectomized female rats (29,30), we hypothesize that NPY decreases the release of LHRH by inhibiting the noradrenergic neurons that have been shown to mediate pulsatile release of LHRH (31,32). Therefore, when the release of NPY is inhibited by leptin, noradrenergic impulses are generated that act on ␣ 1 receptors on the NO-ergic neurons, causing the release of NO, which diffuses to the LHRH terminals and activates LHRH release by activating guanylate cyclase and cyclooxygenase 1 , as shown in our prior experiments (31,32). The LHRH enters the portal vessels and is carried to the anterior pituitary gland, where it acts to stimulate FSH and particularly LH release by combining with its receptors on the gonadotropes.…”

Permanently compromised NADPH-diaphorase activity within the osmotically activated supraoptic nucleus after in utero but not adult exposure to Aroclor 1254

“…osmoregulation, thyroid status, circadian rhythm, nutrient homeostasis, reproduction and growth (Canabal et al, 2007;Ding et al, 1994;Liu et al, 1998;Rettori et al, 1993), Aroclor 1254-induced disruption of NOS activity may represent one mechanism through which PCBs and similarly acting environmental toxicants may affect important regulatory physiological functions governed by the hypothalamus. These functions may include osmoregulatory capacity and blood pressure responses to stress in late adult rats which our lab has shown are significantly impaired by developmental exposure to similar organohalogens (Shah et al, 2011).…”

Colony‐stimulating factors in rapid eye movement sleep and non‐rapid eye movement sleep regulation

“…Nitric oxide is a gas neurotransmitter that regulates neuroendocrine function 6 and most likely controls sleep. 7 The arc is rich in many secretory cells of hypothalamic hormones including luteinizing hormone-releasing hormone and growth hormone-releasing hormone (GHRH).…”