Role of RF-amid Related Peptide-3 (RFRP-3) in Inhibitory Effect of Orexin A on Reproductive Function in the Animal Model of Male Wistar Rats

2019 ◽  
Vol 127 (10) ◽  
pp. 697-705 ◽  
Author(s):  
Jafar Alipoor Hefshejanni ◽  
Homayoun Khazali

Abstract Aims The aim of the present study is to examine the orexin A (OXA) signaling can leave any impact on the hypothalamic-pituitary-gonadal (HPG) axis and this impact can be relayed through the pathway of RF amide-related peptide-3 (RFRP-3, the mammalian ortholog of the avian gonadotropin-inhibitory hormone)/G-protein coupled receptor (GPR)-147 (RFRP-3 receptor) as a novel target for controlling of HPG axis in the male rats. Materials and Methods Male rats were categorized randomly into experimental groups including control vehicle, OXA, and its antagonists’ group and went through to surgical cannulation into the third ventricle. After the intracerebroventricular injection of each solution, blood samples were collected for measurements of the LH and testosterone using radioimmunoassay method. Hypothalamus of the animals were isolated for analysis of the relative expression of Rfrp-3/Gpr-147 along with Gnrh gene by Real time-PCR. Also, in the different cohort of animal sexual behavior test was done. Results It was shown that OXA significantly decreases the mean serum level of the LH and testosterone and, at the same time, its antagonists neutralize this impact. Moreover, we demonstrated that OXA has reduced the hypothalamic gene expression of Gnrh and increased the expression of Rfrp-3 and Gpr-147 genes. While OXA antagonists neutralize this impact. Conclusions The results of this study are related to the impact of orexin on the HPG axis. It is recommended that RFRP-3/GPR-147 system as the interneural pathway relay the data of orexin to the neurons of GnRH.

Author(s):  
Douglas Lopes Almeida ◽  
Gabriel Sergio Fabricio ◽  
Laize Peron Tófolo ◽  
Tatiane Aparecida Ribeiro ◽  
Camila Cristina Ianoni Matiusso ◽  
...  

Abstract Exercise counteracts obesity effects, but information on how early-life obesity may affect long-term adaptation to exercise is lacking. This study investigates the impact of early-life postnatal overfeeding (PO) on animals’ adaptation to exercise. Only male Wistar rats were used. On postnatal day (PN) 30, rats from control (NL-9 pups) or PO (SL-3 pups) litters were separated into four groups: NL-sedentary (NL-Se), NL-exercised (NL-Ex), SL-sedentary (SL-Se), and SL-exercised (SL-Ex). Exercised groups performed moderate-intensity exercise, running on a treadmill, from PN30 to PN90. Further experiments were carried out between PN90 and PN92. PO promoted obesity in SL versus NL rats (P < 0.05). Exercise reduced body weight (P < 0.001), body fat (P < 0.01), and improved glucose homeostasis in SL-Ex versus SL-Se. SL-Ex presented lower VO2max (P < 0.01) and higher post-exercise LDH (P < 0.05) compared to NL-Ex rats. Although moderate exercise counteracted obesity in SL rats, early-life overnutrition restricts fitness gains in adulthood, indicating that early obesity may impair animals’ adaptation to exercise.


2019 ◽  
Vol 4 (4) ◽  
pp. 137-142
Author(s):  
Vahid Azizi ◽  
Shahrbanoo Oryan ◽  
Homayuon Khazali ◽  
Abdolkarim Hosseini

Introduction: The neuropeptide Y (NPY) in the neural circuits of the hypothalamus has a stimulating effect on reproductive activities in mammals. Kisspeptin (KiSS1) is a quintessential neurotransmitter in the reproductive axis which directly stimulates gonadotropin-releasing hormone neurons in the hypothalamus. The distribution of KiSS1 expressing cells in the pituitary was described previously. Despite earlier reports showing the KiSS1 receptor, G-protein coupled receptor 54 (GPR54) expression in the pituitary, the potential physiological roles of kisspeptin at this gland have remained obscure. Accordingly, this study investigated the role of NPY on the relative expression of Kiss1 and Gpr54 genes in the pituitary gland in male Wistar rats. Methods: In general, 20 male Wistar rats weighing 200-250 g in 4 groups (5 in each group) received saline, NPY (2.3 nM), BIBP3226 (NPY receptor antagonist, 7.8 nM), and NPY+ BIBP3226. Then, they received the simultaneous injection of these molecules through the third ventricle of the brain. Finally, the relative mean expressions of Kiss1 and Gpr54 genes in the anterior pituitary were quantitatively analyzed by the real-time polymerase chain reaction. Results: The central injection of NPY increased the relative mean expressions of Kiss1 and Gpr54 genes in the pituitary gland compared to the control group although the injection of BIBP3226 eradicated these effects. However, the gene expression of Gpr54 in the rats receiving NPY coupled with BIBP3226 in hypophysis in comparison to the group receiving only NPY demonstrated a significant reduction (P<0.05). Conclusion: Overall, the central injection of NPY stimulated the gene expression of Kiss1 and Gpr54 in the pituitary gland.


Endocrinology ◽  
2005 ◽  
Vol 146 (2) ◽  
pp. 784-789 ◽  
Author(s):  
Nicolas R. Vulliémoz ◽  
Ennian Xiao ◽  
Linna Xia-Zhang ◽  
Sharon L. Wardlaw ◽  
Michel Ferin

Abstract Agouti-related peptide (AGRP), an endogenous melanocortin receptor antagonist, is a powerful orexigenic peptide when infused centrally. AGRP and neuropeptide Y (NPY), another orexigenic peptide, are colocated within the same neurons in the arcuate nucleus. Both NPY and AGRP mRNA expression increases during food restriction, a condition that is known to suppress the GnRH pulse generator and reproductive function. Although NPY has been shown previously to suppress LH secretion in the ovariectomized monkey, data on AGRP are lacking. In this study, we examined the effect of AGRP infusion into the third ventricle on pulsatile LH release in five adult monkeys. The 8-h protocol included a 3-h intraventricular saline infusion to establish baseline pulsatile LH release, followed by a 5-h infusion of AGRP (83–132) [5 μg/h (n = 1) or 10 μg/h (n = 4)]. In separate experiments, each animal received an 8-h saline treatment as a control. Blood samples were collected every 15 min for LH measurements. Cortisol levels were measured every 45 min. AGRP infusion significantly decreased LH pulse frequency (from a baseline of 0.74 ± 0.07 pulse/h to 0.36 ± 0.12 during AGRP infusion; P &lt; 0.01) and mean LH concentrations (to 41.1 ± 7.5% of baseline by h 5 of AGRP infusion; P &lt; 0.001). LH pulse amplitude was not modified by AGRP treatment. AGRP infusion also significantly increased cortisol release, as previously reported. The data demonstrate that central administration of AGRP inhibits pulsatile LH release in the monkey and suggest that AGRP, like NPY, may mediate the effect of a negative energy balance on the reproductive system by suppressing the GnRH pulse generator.


2010 ◽  
Vol 299 (1) ◽  
pp. E54-E61 ◽  
Author(s):  
J. M. Castellano ◽  
A. H. Bentsen ◽  
M. Romero ◽  
R. Pineda ◽  
F. Ruiz-Pino ◽  
...  

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.


2021 ◽  
Vol 12 (4) ◽  
pp. 2308-2315
Author(s):  
Rachid Mosbah ◽  
Aziez Chettoum ◽  
Alberto Mantovani

Selective serotonin reuptake inhibitors (SSRI) are a class of molecules used in treating depression, anxiety, and mood disorders. Paroxetine (PRT) is one of the most prescribed antidepressants, which has attracted great attention regarding its side effects in recent years.  This study was planned to assess the adverse effects of paroxetine on the biochemical parameters and reproductive system. Fourteen male Wistar rats were randomly allocated into two groups (7 rats for each): control and treated with paroxetine at a dose of 5mg/kg.bw for two weeks. At the end of the experiment, blood was collected from the retro-orbital plexus for measuring the biochemical parameters, whereas the reproductive organs were removed for measuring semen quality and the histological investigations. Results showed that paroxetine induced significant changes in some biochemical parameters and alteration of semen quality, including sperm count, spermatids number and sperm viability, motility and abnormalities. The histopathological examinations of testis and epididymis revealed an alteration of spermatogenesis, cellular disorganization and vacuolization, enlargement of interstitial space, shrinkage and degenerative changes in the epithelium of seminiferous and epididymal tubules with few to nil numbers of spermatozoa in their lumen. In conclusion, paroxetine treatment caused changes in some biochemical parameters and sperm profiles as well as histopathologic effects of reproductive organs.


2021 ◽  
Vol 3 ◽  
Author(s):  
Alexandre Morin ◽  
Lise Van de Beeck ◽  
Emmanuelle Person ◽  
Helene Plamondon

The adolescence period, marked by sexual and brain maturation, has shown sensitivity to various environmental disruptors. Exposure to the xenoestrogen bisphenol A (BPA) is known to alter physiological and behavioral responses although its role at this critical period remains largely unknown. Recent research further suggests biochemical and genomic effects of BPA to be mitigated by various natural compounds, while effects on behavior have not been examined. This study aimed to characterize (1) the effects of dietary BPA during adolescence on endogenous corticosterone (CORT) secretion, emotional behavior, and testosterone (T) in adulthood, and (2) the impact of combined exposure to BPA with hop extracts (Hop), a phytoestrogen with anxiolytic properties. To do so, four groups of male Wistar rats [postnatal day (PND) 28] were administered corn oil (control), BPA (40 mg/kg), hops (40 mg/kg), or BPA-hops by oral gavage for 21 days (PND 28–48). Blood droplets collected on PND 28, 48, and 71 served to measure CORT and T changes. As adults, rats were tested in the elevated plus maze (EPM), the social interaction test, and the forced swim test. Our findings demonstrated elevated anxiety and a trend toward depressive-like behaviors in BPA- compared to hops-exposed rats. However, BPA intake had no impact on basal CORT levels, or adulthood T secretion and sociability. Of note, BPA's anxiogenic effect manifested through decreased EPM open arm entries was abolished by hops co-supplementation. Together, our observations suggest the adolescence period to be less sensitive to deleterious effects of BPA than what has been reported upon gestational and perinatal exposure.


1981 ◽  
Vol 97 (2) ◽  
pp. 213-220 ◽  
Author(s):  
P. T. Männistö ◽  
J. Mattila ◽  
J. Tuomisto

Abstract. The dual role previously suggested for noradrenergic neurons in TRH-TSH regulation was studied in male rats. α-Methyl-p-tyrosine (αMPT) significantly decreased brain noradrenaline (NA) and dopamine (DA) levels 0.5–6 h after the injection. Maximum inhibition of TSH cold-response occurred at 4 h. One h after administration of l-dopa the brain DA (but not NA) level was considerably elevated. TSH cold-response was not significantly changed. The effects of αMPT and Ca-fusarate on the cold-induced TSH secretion were antagonized by neither dihydroxyphenylserine (DOPS; this drug restores NA stores) nor by l-dopa (which restores DA levels). DOPS even potentiated the depressive effect of αMPT and Ca-fusarate. When given into the third ventricle, NA did not modify basal TSH levels but decreased the cold-induced TSH secretion. When infused directly into the median eminence of the medial basal hypothalamus, NA reduced both basal and cold-induced TSH secretion. Pinealectomy decreased the TSH cold-response but NA seemed to retain its ability to inhibit TSH secretion. These results demonstrate that besides the possible stimulatory action on TSH secretion, noradrenergic neurons also have an inhibitory effect outside the blood-brain barrier, possibly in the median eminence.


Endocrinology ◽  
2014 ◽  
Vol 155 (11) ◽  
pp. 4402-4410 ◽  
Author(s):  
Sara R. Jørgensen ◽  
Mille D. Andersen ◽  
Agnete Overgaard ◽  
Jens D. Mikkelsen

Abstract GnRH is a key player in the hypothalamic control of gonadotropin secretion from the anterior pituitary gland. It has been shown that the mammalian counterpart of the avian gonadotropin inhibitory hormone named RFamide-related peptide (RFRP) is expressed in hypothalamic neurons that innervate and inhibit GnRH neurons. The RFRP precursor is processed into 2 mature peptides, RFRP-1 and RFRP-3. These are characterized by a conserved C-terminal motif RF-NH2 but display highly different N termini. Even though the 2 peptides are equally potent in vitro, little is known about their relative distribution and their distinct roles in vivo. In this study, we raised an antiserum selective for RFRP-1 and defined the distribution of RFRP-1-immunoreactive (ir) neurons in the rat brain. Next, we analyzed the level of RFRP-1-ir during postnatal development in males and females and investigated changes in RFRP-1-ir during the estrous cycle. RFRP-1-ir neurons were distributed along the third ventricle from the caudal part of the medial anterior hypothalamus throughout the medial tuberal hypothalamus and were localized in, but mostly in between, the dorsomedial hypothalamic, ventromedial hypothalamic, and arcuate nuclei. The number of RFRP-1-ir neurons and the density of cellular immunoreactivity were unchanged from juvenile to adulthood in male rats during the postnatal development. However, both parameters were significantly increased in female rats from peripuberty to adulthood, demonstrating prominent gender difference in the developmental control of RFRP-1 expression. The percentage of c-Fos-positive RFRP-1-ir neurons was significantly higher in diestrus as compared with proestrus and estrus. In conclusion, we found that adult females, as compared with males, have significantly more RFRP-1-ir per cell, and these cells are regulated during the estrous cycle.


2021 ◽  
Vol 11 (5) ◽  
pp. 13111-13114

Buprenorphine (BUP), a “synthetic opioid”, may cause memory impairment. This investigation aimed to study the impact of BUP on memory function related to acetylcholinesterase (AChE) activity inhibition in male rats. 24 male Wistar rats were randomly divided into three groups; control (C) and two treatment groups BUP (0.3 and 1) (n=8, for each group). BUP (0.3 and 1 mg/kg) was administrated subcutaneously once a day for 30 days. Normal saline 0.9% was injected in to control groups. In the end, animals were anesthetized and decapitated, and their hippocampus was dissected to assess AChE activity. There were no significant differences between the activities of AChE in the hippocampus in BUP-treated animals compared with controls. Besides, the activities of AChE in the BUP 0.3 group and BUP 1 group did not indicate a significant difference. These findings did not confirm the effect of BUP at doses of 0.3 and 1 mg/kg on memory function associated with the AChE activity inhibition.


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