The role of glutamate and nitric oxide in the reproductive neuroendocrine system

2000 ◽  
Vol 78 (3) ◽  
pp. 165-179 ◽  
Author(s):  
Krishnan M Dhandapani ◽  
Darrell W Brann
Keyword(s):  
Nitric Oxide ◽  
Glutamate Receptors ◽  
Recent Work ◽  
Hypothalamic Nuclei ◽  
New Findings ◽  
Gnrh Release ◽  
Glutamate Agonists ◽  
Lh Release ◽  
Reproductive Events

The preovulatory surge of gonadotropin releasing hormone (GnRH) is essential for mammalian reproduction. Recent work has implicated the neurotransmitters glutamate and nitric oxide as having a key role in this process. Large concentrations of glutamate are found in several hypothalamic nuclei known to be important for GnRH release and glutamate receptors are also located in these key hypothalamic nuclei. Administration of glutamate agonists stimulate GnRH and LH release, while glutamate receptor antagonists attenuate the steroid-induced and preovulatory LH surge. Glutamate has also been implicated in the critical processes of puberty, hormone pulsatility, and sexual behavior. Glutamate is believed to elicit many of these effects by activating the release of the gaseous neurotransmitter, nitric oxide (NO). NO potently stimulates GnRH by activating a heme containing enzyme, guanylate cyclase, which in turn leads to increased production of cGMP and GnRH release. Recent work has focused on identifying anchoring and (or) clustering proteins that target glutamate receptors to the synapse and couple the glutamate-NO neurotransmission system. The present review will discuss these new findings, as well as the role of glutamate and nitric oxide in important mammalian reproductive events, with a focus on the hypothalamic control of preovulatory GnRH release. Key words: glutamate, nitric oxide, GnRH, postsynaptic density, hypothalamus.

scholarly journals Characterization of the Role of NKA in the Control of Puberty Onset and Gonadotropin Release in the Female Mouse

Endocrinology ◽  
2019 ◽  
Vol 160 (10) ◽  
pp. 2453-2463 ◽  
Author(s):  
Silvia León ◽  
Chrysanthi Fergani ◽  
Rajae Talbi ◽  
Serap Simavli ◽  
Caroline A Maguire ◽  
...  
Keyword(s):  
Sex Steroids ◽  
Neurokinin A ◽  
Central Control ◽  
Gnrh Release ◽  
Lh Release ◽  
Timing Of Puberty ◽  
Puberty Onset ◽  
Lh Secretion

Abstract The tachykinin neurokinin B (NKB, Tac2) is critical for proper GnRH release in mammals, however, the role of the other tachykinins, such as substance P (SP) and neurokinin A (NKA) in reproduction, is still not well understood. In this study, we demonstrate that NKA controls the timing of puberty onset (similar to NKB and SP) and stimulates LH release in adulthood through NKB-independent (but kisspeptin-dependent) mechanisms in the presence of sex steroids. Furthermore, this is achieved, at least in part, through the autosynaptic activation of Tac1 neurons, which express NK2R (Tacr2), the receptor for NKA. Conversely, in the absence of sex steroids, as observed in ovariectomy, NKA inhibits LH through a mechanism that requires the presence of functional receptors for NKB and dynorphin (NK3R and KOR, respectively). Moreover, the ability of NKA to modulate LH secretion is absent in Kiss1KO mice, suggesting that its action occurs upstream of Kiss1 neurons. Overall, we demonstrate that NKA signaling is a critical component in the central control of reproduction, by contributing to the indirect regulation of kisspeptin release.

Abstract 220: Role of ECM Stiffness in Microvascular Inflammation

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Kaustabh Ghosh ◽  
Harry Scott ◽  
Xiao Yang ◽  
Soroush Ardekani
Keyword(s):  
Nitric Oxide ◽  
Chronic Inflammation ◽  
Leukocyte Adhesion ◽  
Physical Factors ◽  
No Production ◽  
Cardiovascular Tissue ◽  
Enos Activity ◽  
Endothelial Inflammation ◽  
New Findings

Nitric oxide (NO) produced by endothelial nitric oxide synthase (eNOS) is a critical regulator of inflammation as it inhibits leukocyte adhesion to vessel endothelium. Notably, reduced eNOS activity/NO bioavailability and chronic inflammation are key features, and often major determinants, of atherosclerosis and diabetic cardiovascular complications. Past approaches aimed at normalizing eNOS activity have focused primarily on the role of soluble, genetic or shear stress-mediated physical factors. However, extracellular matrix (ECM) mechanics also plays a crucial role in endothelial cell (EC) activation and function. Importantly, tissue mechanics is altered in both atherosclerosis and diabetes that are marked by chronic inflammation and impaired eNOS activity. Thus, we investigated whether there exists a causal relationship between ECM stiffness and eNOS/NO-dependent endothelial inflammation. To test this hypothesis, we cultured ECs on fibronectin-coated elastic substrates of varying stiffness (220 Pa/soft, 1000 Pa/intermediate and 4000 Pa/stiff). EC mechanosensitivity was first confirmed by quantifying the density of actin cytoskeletal filaments, which increased with increasing ECM stiffness. EC-leukocyte adhesion (inflammation) on these substrates, however, followed a biphasic trend where ECs on both 220 Pa (soft) and 4000 Pa (stiff) substrates exhibited greater leukocyte adhesion than those cultured on intermediate 1000 Pa substrates. This biphasic effect of ECM stiffness on endothelial inflammation correlated inversely with levels of eNOS-activation and NO production on these substrates. Consistent with these data, NF-kB activation was enhanced on 220 Pa and 4000 Pa while being suppressed on 1000 Pa substrates. Preliminary data implicate differential levels of calcium influx via mechanosensitive calcium ion channels in this ECM stiffness-dependent eNOS activation and endothelial inflammation. These new findings can potentially lead to superior cardiovascular disease management as they identify ECM stiffness both as a novel therapeutic target for immunomodulatory strategies as well as a key physical design criterion for the development of instructive biomaterials for cardiovascular tissue engineering.

scholarly journals NKB signaling in the posterodorsal medial amygdala stimulates gonadotropin release in a kisspeptin-independent manner in female mice

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Chrysanthi Fergani ◽  
Silvia Leon ◽  
Stephanie L Padilla ◽  
Anne MJ Verstegen ◽  
Richard D Palmiter ◽  
...  
Keyword(s):  
Reproductive Function ◽  
Editorial Note ◽  
Medial Amygdala ◽  
Independent Manner ◽  
Stimulatory Action ◽  
Knock Out ◽  
Gnrh Release ◽  
Lh Release ◽  
Receptor Neurons

Neurokinin B (NKB) signaling is critical for reproduction in all studied species. The existing consensus is that NKB induces GnRH release via kisspeptin (Kiss1) stimulation in the arcuate nucleus. However, the stimulatory action of NKB is dependent on circulating estrogen (E2) levels, without which, NKB inhibits luteinizing hormone (LH) release. Importantly, the evidence supporting the kisspeptin-dependent role of NKB, derives from models of persistent hypogonadal state [e.g. Kiss1r knock-out (KO) mice], with reduced E2 levels. Here, we demonstrate that in the presence of E2, NKB signaling induces LH release in a kisspeptin-independent manner through the activation of NK3R (NKB receptor) neurons in the posterodorsal medial amygdala (MePD). Importantly, we show that chemogenetic activation of MePD Kiss1 neurons induces LH release, however, the stimulatory action of NKB in this area is Kiss1 neuron-independent. These results document the existence of two independent neuronal circuitries within the MePD that regulate reproductive function in females.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (<xref ref-type="decision-letter" rid="SA1">see decision letter</xref>).

scholarly journals Immunohistochemical Evidence for Glutamatergic Regulation of Nesfatin-1 Neurons in the Rat Hypothalamus

2020 ◽  
Vol 10 (9) ◽  
pp. 630 ◽  
Author(s):  
Duygu Gok Yurtseven ◽  
Sema Serter Kocoglu ◽  
Zehra Minbay ◽  
Ozhan Eyigor
Keyword(s):  
Glutamate Receptors ◽  
Glutamate Receptor ◽  
Female Rats ◽  
Glutamate Antagonists ◽  
Male And Female Rats ◽  
Hypothalamic Nuclei ◽  
Glutamate Agonists ◽  
Arcuate Nuclei ◽  
Immunohistochemical Evidence ◽  
Anorexigenic Peptide

Nesfatin-1, identified as an anorexigenic peptide, regulates the energy metabolism by suppressing food intake. The majority of nesfatin-1-synthesizing neurons are concentrated in various hypothalamic nuclei, especially in the supraoptic (SON), arcuate (ARC) and paraventricular nuclei (PVN). We tested the hypothesis that the glutamatergic system regulates nesfatin-1 neurons through glutamate receptors. Therefore, the first aim of the proposed studies was to examine effects of different glutamate agonists in the activation of nesfatin-1 neurons using c-Fos double immunohistochemical labeling. Experimental groups were formed containing male and female rats which received intraperitoneal injections of glutamate agonists kainic acid, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) while the control rats received vehicle. The significant increase in the number of c-Fos-expressing nesfatin-1 neurons after agonist injections were observed both in female and male subjects and some of these effects were found to be sexually dimorphic. In addition, treatment with specific glutamate antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) or dizocilpine (MK-801) before each of the three agonist injections caused a statistically significant reduction in the number of activated nesfatin-1 neurons in the hypothalamic nuclei including supraoptic, paraventricular and arcuate nuclei. The second aim of the study was to determine the expression of glutamate receptor subunit proteins in the nesfatin-1 neurons by using a double immunofluorescence technique. The results showed that the glutamate receptor subunits, which may form homomeric or heteromeric functional receptor channels, were expressed in the nesfatin-1 neurons. In conclusion, the results of this study suggest that nesfatin-1 neurons respond to glutamatergic signals in the form of neuronal activation and that the glutamate receptors that are synthesized by nesfatin-1 neurons may participate in the glutamatergic regulation of these neurons.

scholarly journals Immobilization Induces Acute Nitric Oxide Production in the Rat Hypothalamus: A Role of Ionotropic Glutamate Receptors in the Paraventricular Nucleus

Endocrinology ◽  
2004 ◽  
Vol 145 (8) ◽  
pp. 3603-3607 ◽  
Author(s):  
Tetsuo Shirakawa ◽  
Masato Mitome ◽  
Takashi Kikuiri ◽  
Wataru Nakamura ◽  
Shohei Oshima ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Glutamate Receptors ◽  
Paraventricular Nucleus ◽  
Ionotropic Glutamate Receptors ◽  
Nitric Oxide Production ◽  
Rat Hypothalamus ◽  
Oxide Production

Glutamate is a Fast Excitatory Transmitter at Some Buccal Neuromuscular Synapses in Aplysia

1999 ◽  
Vol 82 (3) ◽  
pp. 1477-1488 ◽  
Author(s):  
Lyle E. Fox ◽  
Philip E. Lloyd
Keyword(s):  
Glutamate Receptors ◽  
Motor Neurons ◽  
Feeding Behaviors ◽  
Effective Agent ◽  
Neuromuscular Synapses ◽  
Cholinergic Antagonist ◽  
Glutamate Agonists ◽  
Excitatory Junction Potentials ◽  
Excitatory Transmitter

Studies of the modulation of synaptic transmission in buccal muscle of Aplysiawere limited because the conventional fast transmitter used by a number of large buccal motor neurons was unknown. Most of the identified buccal motor neurons are cholinergic because they synthesize acetylcholine (ACh) and their excitatory junction potentials (EJPs) are blocked by the cholinergic antagonist hexamethonium. However, three large identified motor neurons (B3, B6, and B38) do not synthesize ACh and their EJPs are not inhibited by hexamethonium. To identify the fast excitatory transmitter used by these noncholinergic motor neurons, we surveyed putative transmitters for their ability to evoke contractions. Of the noncholinergic transmitters tested, glutamate was the most effective at evoking contractions. The pharmacology of the putative glutamate receptor is different from previously characterized glutamate receptors in that glutamate agonists and antagonists previously used to classify glutamate receptors had little effect in this system. In addition, glutamate itself was the most effective agent tested at reducing EJPs evoked by the noncholinergic motor neurons presumably by desensitizing glutamate receptors. Finally, immunocytology using an antiserum raised to conjugated glutamate in parallel with intracellular fills indicated that the varicose axons of these motor neurons were glutamate-immunoreactive. Taken together, these results indicate that the fast transmitter used by the noncholinergic neurons is almost certainly glutamate itself. This information should help us understand the role of transmitters and cotransmitters in the generation of feeding behaviors in Aplysia.

scholarly journals NKB Signaling in the Medial Amygdala Stimulates Gonadotropin Release in a Kisspeptin-Independent Manner in Female Mice

2018 ◽  
Author(s):  
Chrysanthi Fergani ◽  
Silvia León ◽  
Stephanie L. Padilla ◽  
Anne MJ Verstegen ◽  
Richard D. Palmiter ◽  
...  
Keyword(s):  
Arcuate Nucleus ◽  
Reproductive Function ◽  
Medial Amygdala ◽  
Regulatory Pathway ◽  
Neurokinin B ◽  
Independent Manner ◽  
Stimulatory Action ◽  
Gnrh Release ◽  
Lh Release

AbstractNeurokinin B (NKB) signaling is critical for reproduction in all studied species. The existing consensus is that NKB induces GnRH release via kisspeptin (Kiss1) stimulation in the arcuate nucleus. However, the stimulatory action of NKB is dependent on circulating estrogen (E2) levels, without which, NKB inhibits LH release. Importantly, the evidence supporting the kisspeptin-dependent role of NKB, derives from models of persistent hypogonadal state [e.g. Kiss1r knockout (KO) mice], with reduced E2 levels. Here, we demonstrate that in the presence of E2, NKB signaling induces LH release in a kisspeptin-independent manner. Moreover, senktide (NKB receptor agonist) delivery to the medial amygdala (MeA) increases LH in E2-treated Kiss1 KO females (but not males or sham-treated females) similar to controls, and thus, this increase is independent of Kiss1 neurons. These results document a novel kisspeptin-independent regulatory pathway of reproductive function in females mediated by NKB-responsive neurons in the MeA.

Role of glutamate receptors and nitric oxide on the effects of glufosinate ammonium, an organophosphate pesticide, on in vivo dopamine release in rat striatum

Toxicology ◽  
2013 ◽  
Vol 311 (3) ◽  
pp. 154-161 ◽  
Author(s):  
Lilian R.F. Faro ◽  
Brenda V. Ferreira Nunes ◽  
Miguel Alfonso ◽  
Vania M. Ferreira ◽  
Rafael Durán
Keyword(s):  
Nitric Oxide ◽  
Glutamate Receptors ◽  
Dopamine Release ◽  
Rat Striatum ◽  
Organophosphate Pesticide ◽  
Glufosinate Ammonium
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