TY - JOUR AU - Vastagh, Csaba AU - Farkas, Imre AU - Csillag, Veronika AU - Watanabe, Masahiko AU - Kalló, Imre AU - Liposits, Zsolt TI - Cholinergic control of GnRH neuron physiology and luteinizing hormone secretion in male mice: involvement of ACh/GABA co-transmission JF - JOURNAL OF NEUROSCIENCE J2 - J NEUROSCI VL - 44 PY - 2024 IS - 12 PG - 23 SN - 0270-6474 DO - 10.1523/JNEUROSCI.1780-23.2024 UR - https://m2.mtmt.hu/api/publication/34566049 ID - 34566049 N1 - Laboratory of Endocrine Neurobiology, HUN-REN Institute of Experimental Medicine, Budapest, H-1083, Hungary Department of Anatomy, Hokkaido University School of Medicine, Sapporo, 060-8638, Japan Export Date: 22 May 2024 CODEN: JNRSD Chemicals/CAS: 4 aminobutyric acid, 28805-76-7, 56-12-2; acetylcholine, 51-84-3, 60-31-1, 66-23-9; carbachol, 462-58-8, 51-83-2; gonadorelin, 33515-09-2, 9034-40-6; luteinizing hormone, 39341-83-8, 9002-67-9; muscarine, 300-54-9; tetrodotoxin, 4368-28-9, 4664-41-9; nicotine, 54-11-5; Acetylcholine; Carbachol; Cholinergic Agents; gamma-Aminobutyric Acid; Gonadotropin-Releasing Hormone; Luteinizing Hormone; Nicotine Funding details: European Commission, EC Funding text 1: We express our gratitude to Dr. Suzanne M. Moenter (Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan) for the kind donation of the GnRH-GFP transgenic mice used in this study. We are also grateful to Dr. Cathrine Dulac (The Biological Labs, Harvard University, Cambridge, Massachusetts) for the gift of the GnRH-Cre mouse line and to Dr. Erik Hrabovszky (Institute of Experimental Medicine, Budapest, Hungary) for the critical reading of the manuscript and the donation of the GnRH antibody. We appreciate the excellent technical assistance of Ms. Barbara Göblyös and Ms. Katalin Bartosek provided with sampling procedures. We are thankful for the technical support of E. Sipos in the Virus Technology Unit of IEM and P. Vági and L. Barna in the Nikon Microscopy Center at IEM (Nikon Austria and Auro-Science Consulting) and Richárd Sinkó at the Laboratory of Molecular Cell Metabolism of IEM and Levente Kontra at the Central Unit of Bioinformatics of IEM. We also thank Z. Erdélyi, F. Erdélyi, and the staff of the Animal Facility and the Medical Gene Technology Unit of IEM for expert technical help with the breeding and genotyping of the mouse strains used in this study. Project no. RRF-2.3.1-21-2022-00011, titled National Laboratory of Translational Neuroscience, has been implemented with the support provided by the Recovery and Resilience Facility of the European Union within the framework of Programme Széchenyi Plan Plus. National Research, Development and Innovation Office, K128278 and K142357, to Z.L. and K129142, to I.K. Programme Széchenyi Plan Plus, RRF-2.3.1-21-2022-00011, to Z.L. The funder had no role in the design of the study, data collection and interpretation, or the decision to submit the work for publication. *C.V. and I.F. contributed equally to this work. The authors declare no competing financial interests. AB - GnRH-synthesizing neurons orchestrate reproduction centrally. Early studies have proposed the contribution of acetylcholine (ACh) to hypothalamic control of reproduction, although the causal mechanisms haven't been clarified. Here, we report that in vivo pharmacogenetic activation of the cholinergic system increased the secretion of luteinizing hormone (LH) in orchidectomized mice. 3DISCO immunocytochemistry and electron microscopy revealed the innervation of GnRH neurons by cholinergic axons. Retrograde viral labeling initiated from GnRH-Cre neurons identified the medial septum and the diagonal band of Broca as exclusive sites of origin for cholinergic afferents of GnRH neurons. In acute brain slices, ACh and the ACh receptor (AChR) agonist carbachol evoked a biphasic effect on the firing rate in GnRH neurons, first increasing and then diminishing it. In the presence of tetrodotoxin, carbachol induced an inward current, followed by a decline in the frequency of mPSCs, indicating a direct influence on GnRH cells. RT-PCR and whole-cell patch-clamp studies revealed that GnRH neurons expressed both nicotinic (α4β2, α3β4, and α7) and muscarinic (M1-M5) ACh receptors. The nicotinic AChRs contributed to the nicotine-elicited inward current and the rise in firing rate. Muscarine via M1 and M3 receptors increased, while via M2 and M4 reduced the frequency of both miniature postsynaptic currents (mPSCs) and firing. Optogenetic activation of channelrhodopsin-2-tagged cholinergic axons modified GnRH neuronal activity and evoked co-transmission of ACh and GABA from a subpopulation of boutons. These findings confirm that the central cholinergic system immensely regulates GnRH neurons and activates the HPG-axis via ACh and ACh/GABA neurotransmissions in male mice. LA - English DB - MTMT ER - TY - JOUR AU - Kalló, Imre AU - Omrani, Azar AU - Meye, Frank J. AU - de Jong, Han AU - Liposits, Zsolt AU - Adan, Roger A. H. TI - Characterization of orexin input to dopamine neurons of the ventral tegmental area projecting to the medial prefrontal cortex and shell of nucleus accumbens JF - BRAIN STRUCTURE & FUNCTION J2 - BRAIN STRUCT FUNC VL - 227 PY - 2022 IS - 3 SP - 1083 EP - 1098 PG - 16 SN - 1863-2653 DO - 10.1007/s00429-021-02449-8 UR - https://m2.mtmt.hu/api/publication/32600821 ID - 32600821 LA - English DB - MTMT ER - TY - JOUR AU - Vastagh, Csaba AU - Csillag, Veronika AU - Solymosi, Norbert AU - Farkas, Imre AU - Liposits, Zsolt TI - Gonadal Cycle-Dependent Expression of Genes Encoding Peptide-, Growth Factor-, and Orphan G-Protein-Coupled Receptors in Gonadotropin- Releasing Hormone Neurons of Mice JF - FRONTIERS IN MOLECULAR NEUROSCIENCE J2 - FRONT MOL NEUROSCI VL - 13 PY - 2021 PG - 17 SN - 1662-5099 DO - 10.3389/fnmol.2020.594119 UR - https://m2.mtmt.hu/api/publication/31828021 ID - 31828021 N1 - Laboratory of Endocrine Neurobiology, Institute of Experimental Medicine, Budapest, Hungary Faculty of Information Technology and Bionics, Roska Tamás Doctoral School of Sciences and Technology, Pázmány Péter Catholic University, Budapest, Hungary Centre for Bioinformatics, University of Veterinary Medicine, Budapest, Hungary Department of Neuroscience, Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, Budapest, Hungary Cited By :3 Export Date: 6 November 2023 Correspondence Address: Liposits, Z.; Laboratory of Endocrine Neurobiology, Hungary; email: liposits.zsolt@koki.mta.hu Correspondence Address: Liposits, Z.; Department of Neuroscience, Hungary; email: liposits.zsolt@koki.mta.hu Chemicals/CAS: 2 morpholino 8 phenylchromone, 154447-36-6; cholecystokinin, 9011-97-6, 93443-27-7; epidermal growth factor receptor, 79079-06-4; gonadorelin, 33515-09-2, 9034-40-6; growth factor receptor bound protein 2, 148266-08-4; melanocortin 3 receptor, 189235-81-2; mitogen activated protein kinase 1, 137632-08-7; mitogen activated protein kinase 3, 137632-07-6; Muellerian inhibiting factor, 80497-65-0; neuromedin B, 87096-84-2; neuromedin U, 117505-80-3; phosphatidylinositol 3 kinase, 115926-52-8; prolactin, 12585-34-1, 50647-00-2, 9002-62-4; secretin, 1393-25-5, 17034-35-4, 73559-81-6, 108153-74-8; somatomedin C, 67763-96-6; somatostatin, 38916-34-6, 51110-01-1; transforming growth factor beta receptor 1; transforming growth factor beta receptor 2 Tradenames: ly 294002 Funding details: National Research, Development and Innovation Office, NKFI K-115984, NKFI K-128278 Funding text 1: The authors express their gratitude to Dr. Suzanne M. Moenter (Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA) for the kind donation of the GnRH-GFP transgenic mice used in this study. Funding. This study was supported by the National Research, Development and Innovation Office, Hungary (NKFI K-128278, NKFI K-115984). Funding text 2: This study was supported by the National Research, Development and Innovation Office, Hungary (NKFI K-128278, NKFI K-115984). LA - English DB - MTMT ER - TY - JOUR AU - Bálint, Flóra AU - Csillag, Veronika AU - Vastagh, Csaba AU - Liposits, Zsolt AU - Farkas, Imre TI - Insulin-like growth factor 1 (IGF-1) increases GABAergic neurotransmission to GnRH neurons via suppressing the retrograde tonic endocannabinoid signaling pathway in mice. JF - NEUROENDOCRINOLOGY J2 - NEUROENDOCRINOLOGY VL - 111 PY - 2021 IS - 12 SP - 1219 EP - 1230 PG - 12 SN - 0028-3835 DO - 10.1159/000514043 UR - https://m2.mtmt.hu/api/publication/31828015 ID - 31828015 N1 - Institute of Experimental Medicine, Laboratory of Endocrine Neurobiology, Hungarian Academy of Sciences, Szigony u. 43, Budapest, HU-1083, Hungary Roska Tamás Doctoral School of Sciences and Technology, Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, Budapest, Hungary Department of Neuroscience, Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, Budapest, Hungary Cited By :7 Export Date: 5 March 2024 CODEN: NUNDA Correspondence Address: Farkas, I.; Institute of Experimental Medicine, Szigony u. 43, Hungary; email: liposits.zsolt@koki.mta.hu Chemicals/CAS: 1 (2,4 dichlorophenyl) 5 (4 iodophenyl) 4 methyl n (1 piperidyl) 1h pyrazole 3 carboxamide, 183232-66-8; 2 morpholino 8 phenylchromone, 154447-36-6; gonadorelin, 33515-09-2, 9034-40-6; n (1,4 benzodioxan 6 yl) 3 (4 tert butylphenyl)acrylamide, 545395-94-6; phosphatidylinositol 3 kinase, 115926-52-8; picrotoxin, 124-87-8; somatomedin C, 67763-96-6; 4 aminobutyric acid, 28805-76-7, 56-12-2; Endocannabinoids; gamma-Aminobutyric Acid; Gonadotropin-Releasing Hormone; Insulin-Like Growth Factor I; insulin-like growth factor-1, mouse Tradenames: am 251, Sigma; jb 1, Bachem; ly 294002, Sigma Manufacturers: Bachem; Sigma Funding details: National Research, Development and Innovation Office, K115984, K128278 Funding text 1: This research was supported by the National Research, Development and Innovative Office (K115984 and K128278). AB - Hypophysiotropic gonadotropin releasing-hormone (GnRH) neurons orchestrate various physiological events that control the onset of puberty. Previous studies showed that insulin-like growth factor 1 (IGF-1) induces the secretion of GnRH and accelerates the onset of puberty, suggesting a regulatory role of this hormone upon GnRH neurons.To reveal responsiveness of GnRH neurons to IGF-1 and elucidate molecular pathways acting downstream to the IGF-1 receptor (IGF-1R), in vitro electrophysiological experiments were carried out on GnRH-GFP neurons in acute brain slices from prepubertal (23-29 days) and pubertal (50-day) male mice.Administration of IGF-1 (13 nM) significantly increased the firing rate and frequency of spontaneous postsynaptic currents (sPSCs), and that of excitatory GABAergic miniature postsynaptic currents (mPSCs). No GABAergic mPSCs were induced by IGF-1 in the presence of GABAA-R blocker picrotoxin. The increase in the mPSC frequency was prevented by the use of IGF-1R antagonist, JB1 (1 µM) or the intracellularly applied PI3K blocker (LY294002, 50 µM) showing involvement of IGF-1R and PI3K in the mechanism. Blockade of the transient receptor potential vanilloid 1 (TRPV1), an element of the tonic retrograde endocannabinoid machinery by AMG9810 (10 µM) or antagonizing cannabinoid receptor type-1 (CB1) by AM251 (1 µM) abolished the effect.These findings indicate that IGF-1 arrests the tonic retrograde endocannabinoid pathway in GnRH neurons and this disinhibition increases the release of GABA from presynaptic terminals that, in turn, activates GnRH neurons leading to the fine-tuning of the hypothalamo-pituitary-gonadal axis. LA - English DB - MTMT ER - TY - JOUR AU - Vastagh, Csaba AU - Farkas, Imre AU - Scott, Michael M AU - Liposits, Zsolt TI - Networking of glucagon-like peptide-1 axons with GnRH neurons in the basal forebrain of male mice revealed by 3DISCO-based immunocytochemistry and optogenetics. JF - BRAIN STRUCTURE & FUNCTION J2 - BRAIN STRUCT FUNC VL - 226 PY - 2021 IS - 1 SP - 105 EP - 120 PG - 16 SN - 1863-2653 DO - 10.1007/s00429-020-02167-7 UR - https://m2.mtmt.hu/api/publication/31657980 ID - 31657980 AB - Glucagon-like peptide-1 (GLP-1) regulates reproduction centrally, although, the neuroanatomical basis of the process is unknown. Therefore, the putative networking of the central GLP-1 and gonadotropin-releasing hormone (GnRH) systems was addressed in male mice using whole mount immunocytochemistry and optogenetics. Enhanced antibody penetration and optical clearing procedures applied to 500-1000 µm thick basal forebrain slices allowed the simultaneous visualization of the two distinct systems in the basal forebrain. Beaded GLP-1-IR axons innervated about a quarter of GnRH neurons (23.2 ± 1.4%) forming either single or multiple contacts. GnRH dendrites received a more intense GLP-1 innervation (64.6 ± 0.03%) than perikarya (35.4 ± 0.03%). The physiological significance of the innervation was examined by optogenetic activation of channelrhodopsin-2 (ChR2)-expressing axons of preproglucagon (GCG) neurons upon the firing of GnRH neurons by patch clamp electrophysiology in acute brain slices of triple transgenic mice (Gcg-cre/ChR2/GFP-GnRH). High-frequency laser beam stimulation (20 Hz, 10 ms pulse width, 3 mW laser power) of ChR2-expressing GCG axons in the mPOA increased the firing rate of GnRH neurons (by 75 ± 17.3%, p = 0.0007). Application of the GLP-1 receptor antagonist, Exendin-3-(9-39) (1 μM), prior to the photo-stimulation, abolished the facilitatory effect. In contrast, low-frequency trains of laser pulses (0.2 Hz, 60 pulses) had no effect on the spontaneous postsynaptic currents of GnRH neurons. The findings indicate a direct wiring of GLP-1 neurons with GnRH cells which route is excitatory for the GnRH system. The pathway may relay metabolic signals to GnRH neurons and synchronize metabolism with reproduction. LA - English DB - MTMT ER - TY - JOUR AU - Bake, Tina AU - Le May, Marie V. AU - Edvardsson, Christian E. AU - Vogel, Heike AU - Bergström, Ulrika AU - Albers, Marjorie Nicholson AU - Skibicka, Karolina P. AU - Farkas, Imre AU - Liposits, Zsolt AU - Dickson, Suzanne L. TI - Ghrelin Receptor Stimulation of the Lateral Parabrachial Nucleus in Rats Increases Food Intake but not Food Motivation JF - OBESITY J2 - OBESITY VL - 28 PY - 2020 IS - 8 SP - 1503 EP - 1511 PG - 9 SN - 1930-7381 DO - 10.1002/oby.22875 UR - https://m2.mtmt.hu/api/publication/31371873 ID - 31371873 LA - English DB - MTMT ER - TY - JOUR AU - Leiszter, Katalin AU - Udvardyné Galamb, Orsolya AU - Kalmár, Alexandra AU - Zsigrai, Sára AU - Valcz, Gábor AU - Szigeti, Krisztina Andrea AU - Barták, Barbara Kinga AU - Nagy, Zsófia Brigitta AU - Dank, Magdolna AU - Liposits, Zsolt AU - Igaz, Péter AU - Tulassay, Zsolt AU - Molnár, Béla TI - Az ösztrogének lehetséges szerepe a vastagbéldaganatok kialakulásában JF - ORVOSI HETILAP J2 - ORV HETIL VL - 161 PY - 2020 IS - 14 SP - 532 EP - 543 PG - 12 SN - 0030-6002 DO - 10.1556/650.2020.31674 UR - https://m2.mtmt.hu/api/publication/31286495 ID - 31286495 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Leidmaa, Este AU - Gazea, Mary AU - Patchev, Alexandre V AU - Pissioti, Anna AU - Gassen, Nils Christian AU - Kimura, Mayumi AU - Liposits, Zsolt AU - Kalló, Imre AU - Almeida, Osborne F X TI - Blunted leptin sensitivity during hedonic overeating can be reinstated by activating galanin 2 receptors (Gal2R) in the lateral hypothalamus. JF - ACTA PHYSIOLOGICA J2 - ACTA PHYSIOL VL - 228 PY - 2020 IS - 2 SN - 1748-1708 DO - 10.1111/apha.13345 UR - https://m2.mtmt.hu/api/publication/30744376 ID - 30744376 AB - Since foods with high hedonic value are often consumed in excess of energetic needs, this study was designed to identify the mechanisms that may counter anorexigenic signalling in the presence of hedonic foods in lean animals.Mice, in different states of satiety (fed/fasted, or fed/fasted and treated with ghrelin or leptin, respectively), were allowed to choose between high-fat/high-sucrose and standard foods. Intake of each food type and the activity of hypothalamic neuropetidergic neurons that regulate appetite were monitored. In some cases, food choice was monitored in leptin-injected fasted mice that received microinjections of galanin receptor agonists into the lateral hypothalamus.Appetite-stimulating orexin neurons in the lateral hypothalamus are rapidly activated when lean, satiated mice consume a highly palatable food (PF); such activation (upregulated c-Fos expression) occurred even after administration of the anorexigenic hormone leptin and despite intact leptin signalling in the hypothalamus. The ability of leptin to restrain PF eating is restored when a galanin receptor 2 (Gal2R) agonist is injected into the lateral hypothalamus.Hedonically-loaded foods interrupt the inhibitory actions of leptin on orexin neurons and interfere with the homeostatic control of feeding. Overeating of palatable foods can be curtailed in lean animals by activating Gal2R in the lateral hypothalamus. This article is protected by copyright. All rights reserved. LA - English DB - MTMT ER - TY - JOUR AU - Folgueira, Cintia AU - Beiroa, Daniel AU - Porteiro, Begoña AU - Duquenne, Manon AU - Puighermanal, Emma AU - Fondevila, Marcos F AU - Barja-Fernández, Silvia AU - Gallego, Rosalia AU - Hernández-Bautista, René AU - Castelao, Cecilia AU - Senra, Ana AU - Seoane, Patricia AU - Gómez, Noemi AU - Aguiar, Pablo AU - Guallar, Diana AU - Fidalgo, Miguel AU - Romero-Pico, Amparo AU - Adan, Roger AU - Blouet, Clemence AU - Labandeira-García, Jose Luís AU - Jeanrenaud, Françoise AU - Kalló, Imre AU - Liposits, Zsolt AU - Salvador, Javier AU - Prevot, Vincent AU - Dieguez, Carlos AU - Lopez, Miguel AU - Valjent, Emmanuel AU - Frühbeck, Gema AU - Seoane, Luisa M AU - Nogueiras, Ruben TI - Hypothalamic dopamine signaling regulates brown fat thermogenesis. JF - NATURE METABOLISM J2 - NAT METAB VL - 1 PY - 2019 IS - 8 SP - 811 EP - 829 PG - 19 SN - 2522-5812 DO - 10.1038/s42255-019-0099-7 UR - https://m2.mtmt.hu/api/publication/30830798 ID - 30830798 AB - Dopamine signaling is a crucial part of the brain reward system and can affect feeding behavior. Dopamine receptors are also expressed in the hypothalamus, which is known to control energy metabolism in peripheral tissues. Here we show that pharmacological or chemogenetic stimulation of dopamine receptor 2 (D2R) expressing cells in the lateral hypothalamic area (LHA) and the zona incerta (ZI) decreases body weight and stimulates brown fat activity in rodents in a feeding-independent manner. LHA/ZI D2R stimulation requires an intact sympathetic nervous system and orexin system to exert its action and involves inhibition of PI3K in the LHA/ZI. We further demonstrate that, as early as 3 months after onset of treatment, patients treated with the D2R agonist cabergoline experience an increase in energy expenditure that persists for one year, leading to total body weight and fat loss through a prolactin-independent mechanism. Our results may provide a mechanistic explanation for how clinically used D2R agonists act in the CNS to regulate energy balance. LA - English DB - MTMT ER - TY - JOUR AU - Csillag, Veronika AU - Vastagh, Csaba AU - Liposits, Zsolt AU - Farkas, Imre TI - Secretin Regulates Excitatory GABAergic Neurotransmission to GnRH Neurons via Retrograde NO Signaling Pathway in Mice. JF - FRONTIERS IN CELLULAR NEUROSCIENCE J2 - FRONT CELL NEUROSCI VL - 13 PY - 2019 PG - 14 SN - 1662-5102 DO - 10.3389/fncel.2019.00371 UR - https://m2.mtmt.hu/api/publication/30814315 ID - 30814315 N1 - Cited By :6 Export Date: 23 May 2024 Correspondence Address: Farkas, I.; Laboratory of Reproductive Neurobiology, Hungary; email: farkas.imre@koki.mta.hu Chemicals/CAS: cyclic AMP dependent protein kinase; glucagon, 11140-85-5, 62340-29-8, 9007-92-5; gonadorelin, 33515-09-2, 9034-40-6; neuronal nitric oxide synthase, 506430-87-1; nitric oxide, 10102-43-9; secretin, 1393-25-5, 17034-35-4, 73559-81-6, 108153-74-8 Funding details: Magyar Tudományos Akadémia, MTA Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFIH, K115984, K128278 Funding text 1: This work was supported by the National Research, Development and Innovation Office (K115984 and K128278). Funding text 2: The authors thank Dr. Suzanne M. Moenter (Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, United States) for kindly providing the GnRH-GFP transgenic mice. The authors wish to acknowledge Dr. Zolt?n P?terfi (Department of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Hungary) for the thorough reading of the manuscript. Funding. This work was supported by the National Research, Development and Innovation Office (K115984 and K128278). AB - In mammals, reproduction is regulated by a wide range of metabolic hormones that maintain the proper energy balance. In addition to regulating feeding and energy expenditure, these metabolic messengers also modulate the functional performance of the hypothalamic-pituitary-gonadal (HPG) axis. Secretin, a member of the secretin-glucagon-vasoactive intestinal peptide hormone family, has been shown to alter reproduction centrally, although the underlying mechanisms have not been explored yet. In order to elucidate its central action in the neuroendocrine regulation of reproduction, in vitro electrophysiological slice experiments were carried out on GnRH-GFP neurons in male mice. Bath application of secretin (100 nM) significantly increased the frequency of the spontaneous postsynaptic currents (sPSCs) to 118.0 ± 2.64% compared to the control, and that of the GABAergic miniature postsynaptic currents (mPSCs) to 147.6 ± 19.19%. Resting membrane potential became depolarized by 12.74 ± 4.539 mV after secretin treatment. Frequency of evoked action potentials (APs) also increased to 144.3 ± 10.8%. The secretin-triggered elevation of the frequency of mPSCs was prevented by using either a secretin receptor antagonist (3 μM) or intracellularly applied G-protein-coupled receptor blocker (GDP-β-S; 2 mM) supporting the involvement of secretin receptor in the process. Regarding the actions downstream to secretin receptor, intracellular blockade of protein kinase A (PKA) with KT-5720 (2 μM) or intracellular inhibition of the neuronal nitric oxide synthase (nNOS) by NPLA (1 μM) abolished the stimulatory effect of secretin on mPSCs. These data suggest that secretin acts on GnRH neurons via secretin receptors whose activation triggers the cAMP/PKA/nNOS signaling pathway resulting in nitric oxide release and in the presynaptic terminals this retrograde NO machinery regulates the GABAergic input to GnRH neurons. LA - English DB - MTMT ER -