Differential modulation of gonadotropin responses to kisspeptin by aminoacidergic, peptidergic, and nitric oxide neurotransmission

2012 ◽  
Vol 303 (10) ◽  
pp. E1252-E1263 ◽  
Author(s):  
David García-Galiano ◽  
Rafael Pineda ◽  
Juan Roa ◽  
Francisco Ruiz-Pino ◽  
Miguel A. Sánchez-Garrido ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Essential Elements ◽  
Male Rats ◽  
Limited Attention ◽  
Metabotropic Receptors ◽  
Gonadotropin Secretion ◽  
Receptor Inhibition ◽  
Gonadotropic Axis ◽  
Potential Interactions ◽  
The Impact

Kisspeptins (Kp), products of the Kiss1 gene, have emerged as essential elements in the control of GnRH neurons and gonadotropic secretion. However, despite considerable progress in the field, to date limited attention has been paid to elucidate the potential interactions of Kp with other neurotransmitters known to centrally regulate the gonadotropic axis. We characterize herein the impact of manipulations of key aminoacidergic (glutamate and GABA), peptidergic (NKB, Dyn, and MCH), and gaseous [nitric oxide (NO)] neurotransmission on gonadotropin responses to Kp-10 in male rats. Blockade of ionotropic glutamate receptors (of the NMDA and non-NMDA type) variably decreased LH responses to Kp-10, whereas activation of both ionotropic and metabotropic receptors, which enhanced LH and FSH release per se, failed to further increase gonadotropin responses to Kp-10. In fact, coactivation of metabotropic receptors attenuated LH and FSH responses to Kp-10. Selective activation of GABAA receptors decreased Kp-induced gonadotropin secretion, whereas their blockade elicited robust LH and FSH bursts and protracted responses to Kp-10 when combined with GABAB receptor inhibition. Blockade of Dyn signaling (at κ-opioid receptors) enhanced LH responses to Kp-10, whereas activation of Dyn and NKB signaling modestly reduced Kp-induced LH and FSH release. Finally, MCH decreased basal LH secretion and modestly reduced FSH responses to Kp-10, whereas LH responses to Kp-10 were protracted after inhibition of NO synthesis. In summary, we present herein evidence for the putative roles of glutamate, GABA, Dyn, NKB, MCH, and NO in modulating gonadotropic responses to Kp in male rats. Our pharmacological data will help to characterize the central interactions and putative hierarchy of key neuroendocrine pathways involved in the control of the gonadotropic axis.

Selective role of neuropeptide Y receptor subtype Y2 in the control of gonadotropin secretion in the rat

2007 ◽  
Vol 293 (5) ◽  
pp. E1385-E1392 ◽  
Author(s):  
L. Pinilla ◽  
R. Fernández-Fernández ◽  
J. Roa ◽  
J. M. Castellano ◽  
M. Tena-Sempere ◽  
...  
Keyword(s):  
Neuropeptide Y ◽  
Male Rats ◽  
Receptor Subtype ◽  
Central Administration ◽  
Adult Rats ◽  
Gonadotropin Secretion ◽  
Gonadotropic Axis ◽  
The Impact

Different signals with key roles in energy homeostasis regulate the reproductive axis. These include neuropeptide Y and polypeptide YY3-36, whose type Y2 receptor is the most abundant of this family in the brain. We evaluated herein the putative roles of Y2 receptors in the control of gonadotropin secretion by means of central administration of PYY13-36 (agonist of Y2 receptors) and BIIE 0246 (antagonist of Y2 receptors) to intact and orchidectomized male rats. In addition, the ability of PYY13-36 to elicit GnRH and gonadotropin secretion in vitro and the impact of fasting on LH responses to PYY13-36 in vivo were also monitored. Central administration of PYY13-36 significantly decreased the circulating levels of both gonadotropins, an effect that was observed in prepubertal and adult rats. Yet a dual action of Y2 receptors in the control of male gonadotropic axis was evidenced as their activation induced 1) stimulation of gonadotropin responses to GnRH at the pituitary but 2) inhibition of GnRH secretion at the hypothalamus. Antagonization of Y2 receptors failed to modify basal LH secretion in intact males either after being fed ad libitum or after being fasted. In contrast, their central blockade in orchidectomized rats evoked a significant increase in circulating LH and FSH level, suggesting the constitutive activation of Y2 receptor in such stimulated conditions. In summary, our data evidence a complex mode of action of Y2 receptors in the control of gonadotropic axis, with stimulatory and inhibitory actions at different levels of the system that are sensitive to the gonadal status.

Acute inflammation reduces kisspeptin immunoreactivity at the arcuate nucleus and decreases responsiveness to kisspeptin independently of its anorectic effects

2010 ◽  
Vol 299 (1) ◽  
pp. E54-E61 ◽  
Author(s):  
J. M. Castellano ◽  
A. H. Bentsen ◽  
M. Romero ◽  
R. Pineda ◽  
F. Ruiz-Pino ◽  
...  
Keyword(s):  
Food Intake ◽  
Acute Inflammation ◽  
Arcuate Nucleus ◽  
Metabolic Stress ◽  
Reproductive Function ◽  
Male Rats ◽  
Inflammatory Phase ◽  
Gonadotropic Function ◽  
Gonadotropic Axis ◽  
The Impact

Severe inflammatory challenges are frequently coupled to decreased food intake and disruption of reproductive function, the latter via deregulation of different signaling pathways that impinge onto GnRH neurons. Recently, the hypothalamic Kiss1 system, a major gatekeeper of GnRH function, was suggested as potential target for transmitting immune-mediated repression of the gonadotropic axis during acute inflammation, and yet key facets of such a phenomenon remain ill defined. Using lipopolysaccharide S (LPS)-treated male rats as model of inflammation, we document herein the pattern of hypothalamic kisspeptin immunoreactivity (IR) and hormonal responses to kisspeptin during the acute inflammatory phase. LPS injections induced a dramatic but transient drop of serum LH and testosterone levels. Suppression of gonadotropic function was associated with a significant decrease in kisspeptin-IR in the arcuate nucleus (ARC) that was not observed under conditions of metabolic stress induced by 48-h fasting. In addition, absolute responses to kisspeptin-10 (Kp-10), in terms of LH and testosterone secretion, were significantly attenuated in LPS-treated males that also displayed a decrease in food intake and body weight. Yet pair-fed males did not show similar alterations in LH and testosterone secretory responses to Kp-10, whose magnitude was preserved, if not augmented, during food restriction. In summary, our data document the impact of acute inflammation on kisspeptin content at the ARC as key center for the neuroendocrine control of reproduction. Our results also suggest that suppressed gonadotropic function following inflammatory challenges might involve a reduction in absolute responsiveness to kisspeptin that is independent of the anorectic effects of inflammation.

Stimulatory effect of PYY-(3–36) on gonadotropin secretion is potentiated in fasted rats

2006 ◽  
Vol 290 (6) ◽  
pp. E1162-E1171 ◽  
Author(s):  
L. Pinilla ◽  
R. Fernández-Fernández ◽  
E. Vigo ◽  
V. M. Navarro ◽  
J. Roa ◽  
...  
Keyword(s):  
Normal Function ◽  
Male Rats ◽  
Receptor Subtypes ◽  
Central Administration ◽  
Gonadotropin Secretion ◽  
Reproductive Axis ◽  
Npy Receptor ◽  
Gonadotropic Axis ◽  
Agonistic Activity ◽  
Body Energy

Development and normal function of the reproductive axis requires a precise degree of body energy stores. Polypeptide YY-(3–36) [PYY-(3–36)] is a gastrointestinal secreted molecule recently shown to be involved in the control of food intake with agonistic activity on neuropeptide Y (NPY) receptor subtypes Y2 and Y5. Notably, PYY-(3–36) has been recently demonstrated as putative regulator of gonadotropin secretion in the rat. However, the “reproductive” facet of this factor remains to be fully elucidated. In this context, we report herein our analyses of the influence of the nutritional status on the effects of PYY-(3–36) upon GnRH and gonadotropin secretion. The major findings of our study are 1) the stimulatory effect of central administration of PYY-(3–36) on LH secretion was significantly enhanced after fasting and blocked by a GnRH antagonist; 2) besides central effects, PYY-(3–36) elicited LH and FSH secretion directly at the pituitary level, a response that is also augmented by fasting; 3) PYY-(3–36) inhibited GnRH secretion by hypothalamic fragments from male rats fed ad libitum, whereas a significant stimulatory effect was observed after fasting; and 4) the increase in the gonadotropin responsiveness to PYY-(3–36) in fasting was not associated with changes in the expression of Y2 and Y5 receptor genes at hypothalamus and/or pituitary. In conclusion, our study extends our previous observations suggesting a relevant, mostly stimulatory, role of PYY-(3–36) in the control of gonadotropin secretion. Strikingly, such an effect was significantly enhanced by fasting. Considering the proposed decrease in PYY-(3–36) levels after fasting, the possibility that reduced PYY-(3–36) secretion might contribute to defective function of the gonadotropic axis after food deprivation merits further investigation.

Chronic immobilization stress induces anxiety-related behaviors and affects brain essential minerals in male rats

2020 ◽  
pp. 1-8
Author(s):  
Zafer Sahin ◽  
Alpaslan Ozkurkculer ◽  
Omer Faruk Kalkan ◽  
Ahmet Ozkaya ◽  
Aynur Koc ◽  
...  
Keyword(s):  
Immobilization Stress ◽  
Central Area ◽  
Essential Elements ◽  
Male Rats ◽  
Control Group ◽  
Male Wistar Rats ◽  
Swimming Test ◽  
The Brain ◽  
Center Area ◽  
Chronic Immobilization Stress

Abstract. Alterations of essential elements in the brain are associated with the pathophysiology of many neuropsychiatric disorders. It is known that chronic/overwhelming stress may cause some anxiety and/or depression. We aimed to investigate the effects of two different chronic immobilization stress protocols on anxiety-related behaviors and brain minerals. Adult male Wistar rats were divided into 3 groups as follows ( n = 10/group): control, immobilization stress-1 (45 minutes daily for 7-day) and immobilization stress-2 (45 minutes twice a day for 7-day). Stress-related behaviors were evaluated by open field test and forced swimming test. In the immobilization stress-1 and immobilization stress-2 groups, percentage of time spent in the central area (6.38 ± 0.41% and 6.28 ± 1.03% respectively, p < 0.05) and rearing frequency (2.75 ± 0.41 and 3.85 ± 0.46, p < 0.01 and p < 0.05, respectively) were lower, latency to center area (49.11 ± 5.87 s and 44.92 ± 8.04 s, p < 0.01 and p < 0.01, respectively), were higher than the control group (8.65 ± 0.49%, 5.37 ± 0.44 and 15.3 ± 3.32 s, respectively). In the immobilization stress-1 group, zinc (12.65 ± 0.1 ppm, p < 0.001), magnesium (170.4 ± 1.7 ppm, p < 0.005) and phosphate (2.76 ± 0.1 ppm, p < 0.05) levels were lower than the control group (13.87 ± 0.16 ppm, 179.31 ± 1.87 ppm and 3.11 ± 0.06 ppm, respectively). In the immobilization stress-2 group, magnesium (171.56 ± 1.87 ppm, p < 0.05), phosphate (2.44 ± 0.07 ppm, p < 0.001) levels were lower, and manganese (373.68 ± 5.76 ppb, p < 0.001) and copper (2.79 ± 0.15 ppm, p < 0.05) levels were higher than the control group (179.31 ± 1.87 ppm, 3.11 ± 0.06 ppm, 327.25 ± 8.35 ppb and 2.45 ± 0.05 ppm, respectively). Our results indicated that 7-day chronic immobilization stress increased anxiety-related behaviors in both stress groups. Zinc, magnesium, phosphate, copper and manganese levels were affected in the brain.

The Impact of Acupuncture Treatment on Nitric Oxide (NO) in Migraine Patients

2014 ◽  
Vol 39 (3) ◽  
pp. 275-283 ◽  
Author(s):  
Yasemin Gündüztepe ◽  
Setenay Mit ◽  
Ersel Geçioglu ◽  
Neslihan Gurbuz ◽  
Osman Salkacı ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Acupuncture Treatment ◽  
The Impact

scholarly journals Beneficial effect of retigabine on memory in rats receiving ethanol

2020 ◽  
Author(s):  
Ewa Zwierzyńska ◽  
Agata Krupa-Burtnik ◽  
Bogusława Pietrzak
Keyword(s):  
Beneficial Effect ◽  
Fear Conditioning ◽  
Morris Water Maze ◽  
Water Maze ◽  
Experimental Models ◽  
Male Rats ◽  
Ethanol Administration ◽  
Free Access ◽  
Oral Gavage ◽  
The Impact

Abstract Background Retigabine belongs to the novel generation of antiepileptic drugs but its complex mechanism of action causes that the drug might be effective in other diseases, for instance, alcohol dependence. It is known that ethanol abuse impaired the function of brain structures associated with memory and learning such as the hippocampus. In our previous study, retigabine reduced hippocampal changes induced by ethanol in the EEG rhythms in rabbits. This study is focused on the impact of retigabine on memory processes in male rats receiving alcohol. Methods Memory was evaluated in various experimental models: Morris water maze, Contextual, and Cued Fear Conditioning tests. Retigabine was administered for 3 weeks directly to the stomach via oral gavage at a dose of 10 mg/kg. Rats received also 20% ethanol (5 g/kg/day in two doses) via oral gavage for 3 weeks and had free access to 5% ethanol in the afternoon and at night. Morris water maze was performed after 1 and 3 weeks of ethanol administration and after 1 week from the discontinuation of ethanol administration. Contextual and Cued Fear Conditioning tests were carried out after 24 h and 72 h of alcohol discontinuation. Results The drug significantly decreased ethanol-induced memory disturbances during alcohol administration as well as slightly improved learning processes after the discontinuation of ethanol administration. Conclusions This beneficial effect of retigabine-ethanol interaction on memory may be a relevant element of the drug’s impact on the development of addiction.

The impact of exogenous nitric oxide during cardiopulmonary bypass for cardiac surgery

Perfusion ◽  
2021 ◽  
pp. 026765912110148
Author(s):  
Joseph Mc Loughlin ◽  
Lorraine Browne ◽  
John Hinchion
Keyword(s):  
Nitric Oxide ◽  
Systematic Review ◽  
Cardiac Surgery ◽  
Cardiopulmonary Bypass ◽  
Troponin I ◽  
Length Of Hospital Stay ◽  
Cochrane Library ◽  
High Quality Research ◽  
Low Cardiac Output Syndrome ◽  
The Impact

Objectives: Cardiac surgery using cardiopulmonary bypass frequently provokes a systemic inflammatory response syndrome. This can lead to the development of low cardiac output syndrome (LCOS). Both of these can affect morbidity and mortality. This study is a systematic review of the impact of gaseous nitric oxide (gNO), delivered via the cardiopulmonary bypass (CPB) circuit during cardiac surgery, on post-operative outcomes. It aims to summarise the evidence available, to assess the effectiveness of gNO via the CPB circuit on outcomes, and highlight areas of further research needed to develop this hypothesis. Methods: A comprehensive search of Pubmed, Embase, Web of Science and the Cochrane Library was performed in May 2020. Only randomised control trials (RCTs) were considered. Results: Three studies were identified with a total of 274 patients. There was variation in the outcomes measures used across the studies. These studies demonstrate there is evidence that this intervention may contribute towards cardioprotection. Significant reductions in cardiac troponin I (cTnI) levels and lower vasoactive inotrope scores were seen in intervention groups. A high degree of heterogeneity between the studies exists. Meta-analysis of the duration of mechanical ventilation, length of ICU stay and length of hospital stay showed no significant differences. Conclusion: This systematic review explored the findings of three pilot RCTs. Overall the hypothesis that NO delivered via the CPB circuit can provide cardioprotection has been supported by this study. There remains a significant gap in the evidence, further high-quality research is required in both the adult and paediatric populations.

Impact of anti-cancer drugs shortages in oncology and hematology departments in a Moroccan hospital

2021 ◽  
pp. 107815522110082
Author(s):  
Ali Cherif Chefchaouni ◽  
Youssef Moutaouakkil ◽  
Badr Adouani ◽  
Yasmina Tadlaoui ◽  
Jamal Lamsaouri ◽  
...  
Keyword(s):  
Management Plan ◽  
Essential Elements ◽  
Cancer Drugs ◽  
Drug Shortage ◽  
Medical File ◽  
Short Supply ◽  
Drug Shortages ◽  
Non Hodgkin Lymphoma ◽  
Anti Cancer ◽  
The Impact

Introduction Drug shortages have been a growing global problem in recent years. Some of them are of vital necessity and importance for the patient, such as those used to treat pathologies in clinical hematology and oncology departments. The objectives of this study are to determine the impact of anti-cancer drugs shortages on both: treatment and patient in the hematology and oncology departments, to describe the actions that have been put in place to manage the shortages and to survey patients about their perspectives and experiences. Materials and methods It was a prospective, observational study, it took place in the oncology and hematology departments. It was carried out with the help of an operating sheet, which contained two parts: patient and treatment data. This sheet was filled out after the interview with the patient and on the basis of the medical file. Results Of the 101 patients interviewed, 67.3% were impacted by the shortage of drugs. The treated pathology that was most impacted by the rupture was Non-Hodgkin lymphoma (55.8%), vincristine was the drug most responsible for the shortages (34%). Most patients (51.4%) went to a non-local pharmacy to buy the medicine that was in short supply in the hospital. Delayed care was the main impact of the drug shortage (42.6%). As a result of these shortages, the majority of patients (45.6%) were frustrated and anxious about the situation. Conclusion Drug shortages have a profound impact on patient safety, clinical outcomes, quality of treatment, hospital management and other important factors. In-depth collaboration between different health actors and timely communication strategies are essential elements of an effective drug shortage management plan.

Sign in / Sign up

Export Citation Format

Share Document