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Copper (Cu) plays an essential role in the human and animal body system. One of the most important sources of Cu is milk. The purpose of this study was to determine the effect of different doses of injection of inorganic Cu and organic Cu as Cu-arginine and Cu-lysine on Cu concentrations of milk in the lactating Zandi's ewes. This experimental research involved 54 lactating Zandi's ewes collected from the department of State Organization Agriculture of Tehran province, Iran. They were allocated into three main groups included: group 1) which received inorganic form of Cu as copper chloride, groups 2 and 3) which received organic Cu as Cu-arginine or Cu-lysine (25, 50 and 100 mg kg-1 of body weight (BW)) in the chelate form, respectively. The milk samples were taken 30 min before and 6 hours after intravenous injection of Cu preparations. The Cu concentration in milk was measured using the flame atomic absorption spectrometric method. There was no significant difference among the groups in milk's Cu concentration before administration of either inorganic or organic Cu. Data analysis showed that the administration of inorganic Cu caused a significant increase (P<0.01) of Cu concentration in the milk in a dose dependent manner. Furthermore, the administration of Cu-arginine or Cu-lysine in chelate form caused a significant increase (P<0.01) in milk Cu concentration compared to the inorganic Cu. In conclusion, administration of different forms of Cu influenced the Cu concentration in the milk. The organic forms of Cu led to a significant increase in milk Cu concentration in a dose dependent manner compared to the inorganic form of Cu. [ABSTRACT FROM AUTHOR]

Zinc (Zn) plays an essential role in the human and animal body system. Zinc deficiency might cause many disorders, so it is important to provide a sufficient amount of this microelement in both animals and humans. One of the most important sources of Zn is milk. The purpose of this study was to determine whether Zn can pass through the mammary epithelial cell into milk by a cotransport system with amino acid in the lactating ewes. This experimental research included 54 lactating ewes collected from the Agriculture-Jahad Organization of Tehran Province, that were allocated into 9 groups as follows: groups which received inorganic form as Zn chloride (1, 2 and 4 mg/kg), and groups which received organic Zn with different doses of arginine or lysine (1, 2 and 4 mg/kg) in chelate form. Milk samples were taken 30 min before and 6 h after intravenous injection of Zn preparations. Zinc concentration in milk was measured using the flame atomic absorption spectrometric method. There were no significant differences (P>0.05) between groups in Zn concentration of the milk before administration of inorganic or organic Zn. Data analysis showed that administration of inorganic Zn caused a significant increase of Zn concentration in the milk in a dose dependent manner. While administration of arginine or lysine with Zn in chelate form caused a significant decline in Zn concentration of milk compared to inorganic Zn in a dose dependent manner. According to our results, administration of different forms of Zn influenced the Zn concentration in milk. [ABSTRACT FROM AUTHOR]

Objective. The hypothalamic arcuate nucleus proopiomelanocortin (POMC) and neuropeptide Y (NPY) circuitries are involved in the inhibition and stimulation of the appetite, respectively. The aim of this study was to investigate the effects of one-month lasting high-intensity exercise on the POMC mRNA and NPY mRNA expression in the above-mentioned brain structure and appetite and food intake levels.

Balancing identification plays a crucial role in structural dynamics and vibroacoustic system optimization. The followed approach is based on the "Modal testing and Analysis" concept. The Eigen modes of the system model can be visualized and allow a direct physical interpretation. Using the modal models, design improvements can be predicted and the structure optimized. The present paper not only review the test procedure and system identification principles of modal analysis, but also discusses the balancing practical problems with which engineers, performing modal testing and analysis on industrial structures, are confronted on a daily basis. New trends in modal testing and analysis that specifically address these problems are reviewed and illustrated with case studies. This includes the issues of instrumentation, test definition, measurement principles, and parameter estimation. We present here a generalise procedure for solving many of related rotating machine problems. The experimental technique used is called Modal Testing, however the full implementation of Modal Testing in active structures and the implications are not fully understood and are therefore in need of much further and more in depth investigations. The modal parameters of a rotor system with load in the effective length (two discs) was investigated in different applications (before and after added mass), the reaction force in the bearings with different speed of rotation has been studied. The purpose of the study is to develop a multi-methods modal technique, using modal testing in vibration analysis and (FE), it is envisaged that the approach isn't limited to the condition monitoring, has evolved into a standard tool for structural dynamics problem analysis and design optimization. The main objective of the research work presented here is to use the dynamic characteristics help to better understand how the structure will behave and how to adjust or improve the component or system design subsequently a health monitoring approach is investigated for rotor machines applications. [ABSTRACT FROM AUTHOR]

Vibration diagnosis is the most reliable method for identifying machine damage at an early stage. Imbalance and misalignment defects can be detected accurately, as well as rolling bearing damage and gear tooth defects. Satisfactory operation of any machine is always important for tools safety, increased productivity, and low downtime and maintenance overhead. Such requirements could usually be fulfilled by proper design and installation of machines at site. Design part is perhaps more matured in most cases; however installation may play a significant role in the dynamic behaviour even for properly designed machines. Vibration based condition monitoring and codes are well known and widely followed for most of the conventional rotating machines like Pumps, Motors, Turbines, etc., as well as improve or decay shock module in rotor system has been done in this study. The experimental technique used thus far is called Modal Testing, a well known and widely used technique in research and industry to obtain the Modal and Dynamic response properties of structures. The objective of this research using measuring devices to detect incipient damage to rotating components at an early stage. As a result, unplanned downtime can be prevented and maintenance costs can be reduced. [ABSTRACT FROM AUTHOR]

Structural design in the mechanical engineering world involves a wide variety of applications. One aspect of mechanical structures is that they can be used in moving, dynamic situations in rotor system. This can make the design process more complicated, but modern tools in the analytical regime make the engineering process easier. Experimental results indicate invariable fault features embedded in vibration observations can be effectively captured and different fault patterns (for example imbalance, impact and loose foundation) can be correctly classified, both of which imply great potential of the proposed the Spectral chart (Map) Wizard and Modal Testing Data classifier in fault diagnosis of rotor systems that be used in this research. Getting the evolution of a phenomenon with these techniques requires long and repetitive procedures. Waterfall plug-in Spectral Map Wizard adds a new dimension to your results view point. This specific plug-in is able to collect and to synchronize all data coming from the plug-in analyzers in a stack. Results are arranged regarding the different references (RPM, Time, and levels) and represented in 3D or profiles views. The experimental technique used thus far is called Modal Testing; the technique has recently been applied to rotating structures. This paper presents a new method for updating an analytical model using experimental data, by illustrates the results of the experimental modal analysis to provide the best order signal is resample in function of the precise tachometer and then angular domain blocks are converted to the order domain, you will get the right results immediately that could help the designers to have better understanding of rotor performance at the system design stage. [ABSTRACT FROM AUTHOR]

Orexin A and B (OXA and OXB) and their receptors are expressed in the majority of retinal neurons in humans, rats, and mice. Orexins modulate signal transmission between the different layers of the retina. The suprachiasmatic nucleus (SCN) and the retina are central and peripheral components of the body's biological clocks; respectively. The SCN receives photic information from the retina through the retinohypothalamic tract (RHT) to synchronize bodily functions with environmental changes. In present study, we aimed to investigate the impact of inhibiting retinal orexin receptors on the expression of retinal Bmal1 and c-fos, as well as hypothalamic c-fos, Bmal1, Vip, and PACAP at four different time-points (Zeitgeber time; ZT 3, 6, 11, and ZT-0). The intravitreal injection (IVI) of OX1R antagonist (SB-334867) and OX2R antagonist (JNJ-10397049) significantly up-regulated c-fos expression in the retina. Additionally, compared to the control group, the combined injection of SB-334867 and JNJ-10397049 showed a greater increase in retinal expression of this gene. Moreover, the expression of hypothalamic Vip and PACAP was significantly up-regulated in both the SB-334867 and JNJ-10397049 groups. In contrast, the expression of Bmal1 was down-regulated. Furthermore, the expression of hypothalamic c-fos was down-regulated in all groups treated with SB-334867 and JNJ-10397049. Additionally, the study demonstrated that blocking these receptors in the retina resulted in alterations in circadian rhythm parameters such as mesor, amplitude, and acrophase. Finally, it affected the phase of gene expression rhythms in both the retina and hypothalamus, as identified through cosinor analysis and the zero-amplitude test. This study represents the initial exploration of how retinal orexin receptors influence expression of rhythmic genes in the retina and hypothalamus. These findings could provide new insights into how the retina regulates the circadian rhythm in both regions and illuminate the role of the orexinergic system expression within the retina., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Ltd.)

Orexins A and B (OXA and OXB) and their receptors are expressed in the retina of both human and rodents and play a vital role in regulating signal transmission circuits in the retina. There is an anatomical-physiological relationship between the retinal ganglion cells and suprachiasmatic nucleus (SCN) through glutamate as a neurotransmitter and retinal pituitary adenylate cyclase-activating polypeptide (PACAP) as a co-transmitter. SCN is the main brain center for regulating the circadian rhythm, which governs the reproductive axis. The impact of retinal orexin receptors on the hypothalamic-pituitary-gonadal axis has not been investigated. Retinal OX1R or/and OX2R in adult male rats by 3 µl of SB-334867 (1 µg) or/and 3 µl of JNJ-10397049 (2 µg) were antagonized via intravitreal injection (IVI). Four time-periods were considered (3, 6, 12, and 24 h) for the controls without any treatment, SB-334867, JNJ-10397049, and SB-334867 + JNJ-10397049 groups. Antagonizing retinal OX1R or/and OX2R resulted in a significant elevation of retinal PACAP expression compared to control animals. In addition, expression of GnRH increased non-significantly in the hypothalamus over the 6 h of the study, and the serum concentration of LH decreased significantly in the SB-334867 group after 3 h of injection. Furthermore, testosterone serum levels declined significantly, especially within 3 h of injection; serum levels of progesterone were also exposed to a significant rise at least within 3 h of injection. However, the retinal PACAP expression changes were mediated by OX1R more effectively than by OX2R. In this study, we report the retinal orexins and their receptors as light-independent factors by which the retina affects the hypothalamic-pituitary-gonadal axis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Background: Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder without definitive treatments. Orexin and Substance-P (SP) neuropeptides can affect the ovarian steroidogenesis. Moreover, there are limited studies about the role of these neuropeptides in PCOS. We aimed here to clarify the effects of orexins and SP in PCOS as well as any possible interactions between them., Methods: For this purpose, the animals (n = five rats per group) received intraperitoneally a single dose of SB-334,867-A (orexin-1 receptor antagonist; OX1Ra), JNJ-10,397,049 (orexin-2 receptor antagonist; OX2Ra), and CP-96,345 (neurokinin-1 receptor antagonist; NK1Ra), alone or in combination with each other after two months of PCOS induction. The blocking of orexin and SP receptors was studied in terms of ovarian histology, hormonal changes, and gene expression of ovarian steroidogenic enzymes., Results: The antagonists' treatment did not significantly affect the formation of ovarian cysts. In the PCOS groups, the co-administration of OX1Ra and OX2Ra as well as their simultaneous injections with NK1Ra significantly reversed testosterone levels and Cyp19a1 gene expression when compared to the PCOS control group. There were no significant interactions between the PCOS groups that received NK1Ra together with one or both OX1R- and OX2R-antagonists., Conclusion: The blocking of the orexin receptors modulates abnormal ovarian steroidogenesis in the PCOS model of rats. This suggests that the binding of orexin-A and -B to their receptors reduces Cyp19a1 gene expression while increasing testosterone levels., (© 2023. The Author(s).)

Introduction: Endocrine disorders such as polycystic ovary syndrome (PCOS) and hypothyroidism can cause infertility. There are evidence that they happen jointly in some circumstances. It still remains unknown, how these two illnesses interact and influence the body., Methods: Accordingly, a five-group was designed, first is the control group, followed by the PCOS group. Estradiol valerate (EV) induced PCOS, the second group had only PCOS and the third, fourth and fifth groups were given varied dosages of propylthiouracil (PTU) to cause hypothyroidism after induction of PCOS. Steroidogenic acute regulatory protein (StAR) expression was measured in the ovaries, and serum was obtained to determine testosterone levels, as well as superoxide dismutase (SOD) as an antioxidant and malondialdehyde (MDA) as an oxidant., Results: Based on radioimmunoassay data, testosterone levels were significantly higher in the PCOS group than the control group, and significantly lower (p ˂ .05) in PTU groups comparing with the PCOS group. According to the quantitative real-time polymerase chain reaction (qRT-PCR) data, the same results were obtained for the StAR gene as well. The data also indicated a positive correlation between these two. Although both oxidant and antioxidant level increased in PCOS group compared than control group, after hypothyroidism, oxidant level increased significantly (p ˂ .05), meanwhile antioxidant level decreased significantly (p ˂ .05)., Conclusions: The results of this study illustrate that the presence of both PCOS and hypothyroidism alters the situation more than just PCOS. They also indicate that this situation is associated with imbalanced oxidative/antioxidative status., (© 2022 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

Kisspeptin is a hypothalamic peptide which stimulates hypothalamus- pituitary- gonadal (HPG) axis. Morphine is an alkaloid which suppresses reproduction. Ghrelin and leptin are metabolic peptides which play role in relaying information to the HPG axis. In the present study, the interaction effects of kisspeptin and morphine were investigated on plasma and gene expression levels of leptin and ghrelin . Twenty adult male Wistar rats randomized in four groups were received injection of saline, kisspeptin (1.00 nmol), morphine (5.00 mg kg -1 ) or Kisspeptin + morphine. Rats were received kisspeptin and morphine via third cerebral ventricular and subcutaneous injection, respectively. Ten male rats in two groups were received intravenous injection of saline or kisspeptin (7.50 nmol). Blood samples, hypothalamic and adipose tissue samples were collected. Plasma and gene expression levels of ghrelin and leptin were measured using the methods of enzyme-linked immunosorbent assay and real time-PCR, respectively. Morphine significantly increased plasma concentration and hypothalamic mRNA levels of ghrelin compared to saline while kisspeptin significantly decreased them compared to saline. Morphine significantly decreased plasma and mRNA levels of leptin in adipose tissue compared to saline, however, kisspeptin did not increase plasma and mRNA levels of leptin in adipose tissue compared to saline. Kisspeptin significantly decreased the effects of morphine on plasma concentration and hypothalamic gene expression levels of ghrelin compared to morphine alone, however, it did not affect morphine influence on plasma and leptin gene expression levels compared to morphine alone. Kisspeptin and morphine might partly be involved in the regulation of reproductive activity via regulation the metabolic hormones synthesis., Competing Interests: The authors declare no conflict of interest., (© 2022 Urmia University. All rights reserved.)

Background: Polycystic ovary syndrome (PCOS) is a complex heterogeneous disease with various symptoms, which can affect females of reproductive age. Endocrine and metabolic abnormalities such as infertility, being overweight or obese, type 2 diabetes, hyperandrogenism and increased luteinizing hormone (LH) are common in women with PCOS., Objective: This review aimed to assess the efficacy of non-chemical and herbal substances for PCOS recovery., Materials and Methods: The keywords "non-chemical treatment", "herbal treatment", "polycystic ovary syndrome" and "PCOS" were used to search for articles in the electronic databases PubMed/MEDLINE, Web of Science, Scopus, and Reaxys, published from January 2009 to December 2019., Results: 34 relevant studies were found and were briefly described in this review. The most effective herbal treatments in animal models of PCOS were used to restore abnormality in serum sex steroid profile, LH: follicle stimulating hormone ratio, steroidogenic enzymes, cardiovascular parameters, lipid profile, and glucose and estrous cycles. In PCOS patients, positive effects on PCOS due to reductions in testosterone, estrogen, LH, LH: follicle stimulating hormone ratio, and insulin levels were observed., Conclusion: The results of this reviewrevealed the variability and efficacy of phytotherapy and non-chemical treatments associated with PCOS disease. These findings may help future studies on the etiology and treatment of this syndrome., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2022 Azin and Khazali.)

Monosodium glutamate (MSG) is a flavour enhancer that is used as a food additive (E621) in many parts of the world, especially in East Asian countries. However, in recent studies, it has been used as a neurotoxin because MSG is reported to cause neural degeneration in the hypothalamic arcuate of neonatal animals. The results of several studies show the negative effects of MSG injections on different parts of the hypothalamic-pituitary-gonadal (HPG) axis, in addition to its ability to inhibit secretion many reproductive neuropeptides, neurotrophic factors, and hormones, all of which play vital roles in the regulation of reproductive function. Oral administration or injection of large quantities of MSG into newborn animals results in a decrease in or overabundance of the production of many regulatory peptides of the male and female reproductive systems. In this review, we summarize the results of the most important studies that have examined the effect of oral consumption or injection of MSG on regulatory peptides of the HPG axis., Competing Interests: The authors declare no conflicts of interest., (Copyright© by Royan Institute. All rights reserved.)

Background: Memory-dependent psychological behaviors have an important role in life. Memory strengthening in adulthood to prevent its defects in aging is a significant issue. The ghrelin endogenous hormone improves memory by targeting glutamatergic and serotonergic circuits. Also, citicoline, a memory strengthening drug in aging, is not recommended to adults due to its side effects. The current study aims to test that ghrelin treatment, like citicoline, would improve passive avoidance memory via expression of the genes encoding the N-methyl-D-aspartate receptor ( NMDAR1 ) and the serotonin receptor 1A ( HTR1α ) involved in this process., Methods: Five groups of adult male rats received (1) saline (as control), (2) 0.5 mg/kg citicoline, or (3-5) 0.3, 1.5, and 3 nmol/μl ghrelin). The rats received the drugs via intra-hippocampal injection. Passive avoidance memory was determined using a shuttle box device. The latency to enter the dark chamber before (IL) and after (RL) injection and the total duration of the animal's presence in the light compartment (TLC) were evaluated. Then, the gene expression rates of NMDAR1 and HTR1α were measured by the Real-Time PCR., Results: Ghrelin and citicoline had some similar and significant effects on passive avoidance memory, and both increased NMDAR1 and decreased HTR1α expression., Conclusion: Ghrelin, like citicoline, improves passive avoidance learning by altering the NMDAR1 and HTR1α expression in the hippocampus.

Aims: A number of studies have shown that neuropeptide Y (NPY) is considered to be one of the key regulators of hypothalamic-pituitary-gonadal (HPG) axis in the mammals. In addition, kisspeptin (encode by Kiss1 gene), neurokinin B (encode by Tac3 gene) and dynorphin (encode by Pdyn gene) (commonly known as KNDy secreting neurons) are a powerful upstream regulators of GnRH neuron in hypothalamus., Materials and Methods: The present study aims to investigate the effects of the intracerebroventricular (icv) injection of NPY and BIBP3226 (NPY receptor antagonist (NPYRA)) on the male sexual behavioral. Additionally, in order to see whether NPY signals can be relayed through the pathway of kisspeptin/neurokinin B/dynorphin, the gene expression of these peptides along with Gnrh1 gene in the hypothalamus were measured., Results: The icv injection of NPY decreased the latencies and increase the frequencies of sexual parameters of the male rats in a significant way. In this line, NPYRA antagonized the stimulative effects of NPY. Moreover, data from real-time quantitative PCR indicated that injection of NPY significantly increased the gene expression of Gnrh1 , Kiss1 and Tac3 and decrease the Pdyn while treatment with NPYRA controlled the modulative effects of NPY on these gene expression., Conclusions: In conclusion based on the results of this study, NPY can exert its impacts on the sexual behavior of male rats via modulation of the KNDy secreting neurons as an interneural pathway to GnRH neurons.

RFamide-related peptide-3 (RFRP-3) has been postulated as the suppressor of the reproductive axis at hypothalamic, pituitary and gonadal levels. Considering the hypothalamic level, RFRP-3 can suppress the activity of gonadotropin-releasing hormone (GnRH) neurons and their upstream neuronal stimulator, namely; the kisspeptin neurons. The effects of the RFRP-3 on the other regulators of GnRH neurons, however, are not completely investigated. Furthermore, substance P (SP) has been known as one of the coordinators of GnRH/ luteinizing hormone (LH) and the kisspeptin/G protein-coupled receptor 54 (GPR54) systems. The present study was aimed at investigating the impacts of RFRP-3 on the effects of SP on the reproductive performance in ovariectomized female rats. After intracerebroventricular (ICV) cannulation, the rats were subjected to the ICV injection of either SP or RFRP-3 and simultaneous injection of them and their selective antagonists. Blood and hypothalamic samplings and also sexual behavioral test were carried out on two main groups of rats. The analyses of the results of LH radioimmunoassay, gene expression assay for hypothalamic Gnrh1, Kisspeptin and Gpr54 accompanied by sexual behavioral examination revealed that the SP administration promotes reproductive behavior and GnRH/LH system and upregulates Kisspeptin expression. The RFRP-3 administration suppressed reproductive behavior, GnRH / LH system and Kisspeptin expression; however, the simultaneous injection of SP and RFRP-3 was devoid of significant alterations in the assessed parameters. The results showed that RFRP-3 can modulates the impacts of SP on the reproductive performance in ovariectomized female rats in part through adjusting Kisspeptin expression.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, which is associated with increased androgens, chronic inflammation, and oxidative stress. Current research aims at determining the effect of flavonoid apigenin on the level of antioxidant and anti-inflammatory factors in ovarian tissue of rats with PCOS. In this study, 32 female Wistar rats were divided into four groups ( n  = 8): control, PCOS control, and treated groups (20 and 40 mg/kg apigenin). After 21 days of intervention, the serum levels of sex hormones and gonadotropins were measured. The ovarian tissue was removed for biochemical and histological studies. Research findings indicated that apigenin causes significant decrease in estrogen, testosterone levels, LH and LH to FSH ratio, and significant increase in progesterone and FSH levels in serum of treated groups compared to PCOS control group. Different doses of apigenin significantly decreased the inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and total oxidative status (TOS). The total antioxidant capacity (TAC) and superoxide dismutase (SOD) activity significantly increased in treated groups compared to the PCOS control group. The histological results indicated that the number of cysts and theca layer thickness significantly decreased and the number of corpora lutea and granulosa layer thickness significantly increased in the rats receiving the apigenin as compared to the PCOS control group. Flavonoid apigenin through antioxidant and anti-inflammatory properties can be used as an alternative method for treating patients with PCOS.

Several studies have shown that neuropeptide Y (NPY) is considered to be one of the key regulators of the hypothalamic-pituitary-gonadal axis in the mammals. Also, kisspeptin is a powerful upstream regulator of gonadotropin-releasing hormone neurons in the hypothalamus. The present study aims to investigate the effects of the intracerebroventricular (ICV) injection of NPY and BIBP3226 (NPY receptor antagonist) on the reproductive axis (either hormonal or behavioral) of the male rats. Furthermore, to see whether NPY signals can be relayed through the pathway of KiSS1/GPR54 , the gene expression of these peptides in the arcuate nucleus was measured. The ICV injection of NPY decreased the latencies and increased the frequencies of sexual parameters of the male rats in a significant way. Results obtained from LH and testosterone measurement showed that NPY had a significant increase in comparison with the control group. In this line, BIBP3226 antagonized the stimulative effects of NPY. Furthermore, data from real-time quantitative PCR showed that injection of NPY significantly increased the gene expression of KiSS1 and GPR54 , while treatment with BIBP3226 controlled the stimulative effects of NPY on gene expression of KiSS1 and GPR54 . Summing up, NPY can exert its impacts on the reproductive axis, this occurs at least partly through affecting KiSS1/GPR54 system., (© 2020 Urmia University. All rights reserved.)

A functional role of the neuropeptide galanin, executed through the three G-protein coupled receptor subtypes GAL₁₋₃, has been demonstrated in many biological systems and under pathological circumstances. Galanin is involved in many central and peripheral actions, in particular associated with endocrine mechanisms such as anterior pituitary hormone regulation, reproduction, glucose metabolism and also inflammation. The role of galanin in the pathology of the polycystic ovary syndrome (PCOS) and possible therapeutic effects are unknown. However, based on the well known neuroendocrine changes in PCOS patients, it may be assumed that galanin via effects on gonadotropin-releasing hormone (GnRH) secretory neurons could play a significant role in the development of PCOS. The aim of this study was to examine possible therapeutic effects of galanin on hormonal, metabolic and molecular parameters in PCOS. Accordingly, intraperitoneal injection of galanin in a dose- dependent manner in female PCOS rats induced a significant reduction in inflammatory markers (TNF-α, IL-6), an increase in FSH and a decrease in LH, insulin and testosterone (using ELISA kit) compared to the PCOS groups. Moreover, data from real-time quantitative PCR showed significantly ameliorated changes in the mRNA levels of the steroidogenic acute regulatory protein (StAR) and aromatase cytochrome P450 (CYP19). Taken together, galanin has neuroendocrine, anti- and pro-inflammatory and metabolic effects, and we therefore suggest that treatment with this peptide could represent new therapeutic approach for managing hormonal and metabolic disturbances in the PCOS disease., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: Kisspeptin and opioids are important factors for controlling GnRH/LH secretion. In present study, influences of kisspeptin or morphine were investigated on 5α- reductase or aromatase ( CYP19 ) genes expression in the hypothalamus, testis and liver. It aimed to investigate whether kisspeptin pathway may control morphine effects on plasma concentration of testosterone., Materials and Methods: Twenty adult male rats in four groups received saline/saline, kisspeptin (1 nmol)/saline, morphine (5 mg/kg)/saline or kisspeptin/morphine respectively. Mean relative 5α-reductase and aromatase mRNA levels were determined by RT-PCR., Results: Morphine/saline injection increased significantly mean relative mRNA levels of hypothalamic 5α-reductase or aromatase compared to saline/saline. While morphine/saline did not alter mRNA levels of them compared to saline/saline group in the testis and liver. Kisspeptin/saline did not significantly decrease mean relative 5α-reductase or aromatase genes expression compared to saline/saline group in the hypothalamus, testis and liver. Injections of kisspeptin/morphine did not significantly decrease mean relative 5α-reductase or aromatase genes expression compared to morphine/saline group., Conclusion: Up-regulation of hypothalamic 5α-reductase or aromatase mRNA levels may partly induce the inhibitory effects of morphine on GnRH/LH release. Different effects of morphine on aromatase or 5α- reductase genes expression levels in the liver and testis compared to brain may be partly due to different sensitivity or functions of them to morphine used dose., Competing Interests: The authors have nothing to disclose. There is no conflict of interest in this article.

Polycystic ovary syndrome (PCOS) is a proinflammatory/oxidative state resulting in metabolic dysregulation and ovarian dysfunction. Isoflavones in soybean seed possess anti-inflammatory/antioxidant properties. So, in this study, the effects of soybean isoflavone-aglycones on tissue inflammation, oxidative status, and ovarian histology in an animal model of PCOS were considered to achieve a novel therapeutic agent. Thirty-two female Wistar rats were divided into four groups ( n  = 8): a control group receiving the vehicle (CON-); a group with PCOS receiving no treatment (PCOS); and two groups of PCOS rats treated with soybean isoflavone-aglycone fraction (SISAF) at 50 and 100 mg/kg (SISAF50 and SISAF100). PCOS was induced by injecting a single dose of estradiol valerate (4 mg/kg, IM) dissolved in 0.2 ml of sesame oil following 60 days for the full development of polycystic ovaries. The SISAF treatments were administered orally once a day for 21 days. Then, the ovaries were harvested for the assessment of oxidative/antioxidative parameters, interleukin (IL)-6, and tumor necrosis factor (TNF)-α levels concomitant with histological studies. Treatment with SISAF reduced the number of cystic follicles and thickness of the theca layer, as well as increasing the number of corpora lutea and granulosa cells in PCOS rats. Also, SISAF treatment significantly decreased ovarian tissue IL-6 and TNF-α levels, and improved total oxidative/antioxidative status compared to the PCOS group. Isoflavones may provide therapeutic effects in PCOS owing to the antioxidant and anti-inflammatory properties.

Obviously, opiates (e.g., morphine) are associated with the suppression and dysfunction of reproductive axis. It has been reported that substance P (SP) and RF-amid-related peptide-3 (RFRP-3) can exhibit anti-opioid effects in some regions of the nervous system. Moreover, SP and RFRP-3 are deemed as neuropeptides which exert modulatory and regulatory impacts on the function of the reproductive axis. The precise interactions of morphine with SP or RFRP-3 on the parameters of the reproductive activity, however, are not fully known. The present study was aimed to determine the impacts of the interaction of morphine either with SP or RFRP-3 on the hormonal and behavioral parameters of reproductive activity in male rats. In addition, it was aimed at determining whether the effects of these interactions rely on kisspeptin/G protein coupled receptor 54 (GPR54) pathway as the main upstream pulse generator and the mediator of the function of many inputs of gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) system or not. Altogether, the resulted data from the sexual behavior tests, radioimmunoassay of LH/testosterone, and real-time quantitative PCR for the assessment of the expression of hypothalamic Kiss1, Gpr54, and Gnrh1 genes following concomitant administration of morphine with SP or RFRP-3 revealed that the suppressing effects of morphine on the parameters of reproductive axis activity can be affected by the administration of either RFRP-3 or SP. It is advocated that SP and RFRP-3, by the modulation of the expression of hypothalamic Kiss1, can possibly antagonize the effects of morphine on GnRH/LH system and sexual behavior.

Mature spermatozoa contain a whole repertoire of the various classes of cellular RNAs, both coding and non-coding. It was hypothesized that after fertilization they might impact development, a claim supported by experimental evidence in various systems. Despite the current increasing interest in the transgenerational maintenance of epigenetic traits and their possible determination by RNAs, little remains known about conservation in sperm and across generations and the specificities and mechanisms involved in transgenerational maintenance. We identified two distinct fractions of RNAs in mature mouse sperm, one readily extracted in the aqueous phase of the classical TRIzol procedure and a distinct fraction hybridized with homologous DNA in DNA-RNA complexes recovered from the interface, purified after DNase hydrolysis and analyzed by RNA-seq methodology. This DNA-associated RNA (D RNA) was found to represent as much as half of the cell contents in differentiated sperm, in which a major part of the cytoplasmic material has been discarded. Stable complexes were purified free of proteins and identified as hybrids (R-loops) on the basis of their sensitivity to RNase H hydrolysis. Further analysis by RNA-seq identified transcripts from all the coding and non-coding regions of the genome, thus revealing an extensive wave of transcription, prior to or concomitant with the terminal compaction of the chromatin.

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., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objectives: Several pathological conditions are associated with hyper-production of testosterone; however, its impacts are not well understood. Hence, we evaluated the effects of supraphysiological levels of testosterone on gonadotropin-releasing hormone (GnRH) system in the hypothalamus of male rats. Also, we assessed the expression of two excitatory (kisspeptin and neurokinin-B) and two inhibitory (dynorphin and RFamide-related-peptide) neuropeptides upstream of GnRH neurons as possible routes to relay androgen information., Materials and Methods: Gonadectomized (GDX) male rats received single injection of 100, 250 or 500 mg/kg testosterone undecanoate and three weeks later, posterior (PH) and anterior (AH) hypothalamus was dissected for evaluation of target genes using quantitative RT-PCR., Results: We found that GnRH mRNA in the PH was high in GDX rats and 500 mg/kg testosterone reduced GnRH level expression. Finding revealed extremely high level of Kiss1 mRNA in the PH of GDX rats. However, in GDX rats treated with different levels of testosterone, Kiss1 expression was not significantly different than control. We also found that testosterone replacement increased the Kiss1 mRNA level in the AH. Moreover, neurokinin-B mRNA level in PH of GDX rats was similar to control. However, excess testosterone levels were effective in significantly inducing the down-regulation of neurokinin-B expression. The basal level of dynorphin mRNA was increased following testosterone treatments in the AH, where we found no significant difference in the level of RFamide-related-peptide mRNA between the experimental groups., Conclusion: Excess levels of testosterone could act differently from its physiological concentration to regulate hypothalamic androgen sensitive neurons to control GnRH cell., Competing Interests: The authors declare that they have no conflict of interest.

It is an established fact that orexin plays an important role in regulating the reproductive axis and the secretions of gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH). However, its precise cellular and molecular mechanisms are not fully recognized. Accordingly, the aim of the present study is to find out whether the central injection of orexin A (OXA) and its antagonists, SB-334867 (as orexin receptor antagonist 1; OX1RA) and JNJ-10397049 (as orexin receptor antagonist 2; OX2RA), either alone or in combination, can leave any impact on the reproductive axis (either hormonal or behavioral) in the male Wistar rats. Furthermore, in order to see whether OXA signals can be relayed through the pathway of kisspeptin/neurokinin B/dynorphin (known as KNDy neurons, a neural network which works upstream of GnRH neurons) or not, the relative gene expression of these neuropeptides were measured. Overall, the data from radioimmunoassay revealed that OXA significantly decreases the mean serum level of LH and testosterone and, in a similar vein, its antagonists neutralize this impact. Moreover, data from real-time quantitative PCR indicated that OXA has significantly reduced the hypothalamic expression of Gnrh. In this line, the gene expressions of Kisspeptin and Neurokinin b decreased. However, OXA antagonists neutralize this impact. Also, the expression of Dynorphin gene was upregulated by the following application of the OXA. The results of this study are related to the impact of orexin on the reproductive axis. It is recommended that KNDy neurons as the interneural pathway relay the information of orexin to the GnRH neurons.

The essential role of regular physical activity has been emphasized for maintaining a healthy life. However, unfortunately, during the last few decades, the lifestyle of people has led to a decrease in physical activity. Research studies have shown that exercise of different intensities is applied on reproductive performance indices, luteinizing hormone (LH) and testosterone (T), with different effects. Nevertheless, the molecular and cellular mechanisms underlying its function are not completely understood. Therefore, this study aimed to evaluate the role of kisspeptin, neurokinin-B and pro-dynorphin (KNDY) gene-expression changes located in the upstream of GnRH neurons in transferring the effects of different long-term exercise intensities on male reproductive axis. Twenty-one adult Wistar rats were randomly divided into control, 6-month regular moderate exercise (RME-6) and 6-month regular intensive exercise (RIE-6). In moderate and intensive exercise groups, rats were treated 5 days a week for 60 min, at 22 and 35 m/min, respectively. Finally, the hypothalamic arcuate nucleus was isolated and the relative gene expression of kisspeptin (Kiss1), neurokinin-B (Nkb), pro-dynorphin (Pdyn) and gonadotropin-releasing hormone (Gnrh) genes were measured by realtime polymerase chain reaction method. The results showed that RIE-6 treatment decreased Gnrh and increased Pdyn mRNA levels in the arcuate nucleus. Furthermore, although RME-6 treatment decreased Nkb and increased Pdyn mRNA levels, the Gnrh mRNAwas not affected. Regarding the Gnrh mRNA levels and serum concentrations of reproductive indices (LH and T), moderate exercise did not impose harmful effects on the hypothalamic-pituitary-gonadal axis than intensive exercise. The different impacts of diverse long-term exercise intensities on the male pituitary-gonadal axis maybe relay by the various changes in hypothalamic Nkb and Pdyn gene expressions.

Background: Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects 6-10% of women in reproductive age. The medicinal values of Citrullus colocynthis (CCT) extract stems from its anti-oxidative and anti-inflammatory effects. This study evaluated the comparative effect of CCT and metformin on morphometric ovarian disorders in PCOS rats., Materials and Methods: Fifty female Wistar rats having 2-3 consecutive estrous cycles during two weeks were divided into five groups (n=10 each group). The rats in the control group only received sesame oil as estradiol valerate solvent, whereas the rats in the sham group were injected intramuscularly with 4 mg/rat estradiol valerate-induced PCOS. Following PCOS induction, the rats in the metformin group received 50 mg/kg metformin orally for three weeks. Rats in the Extract group were treated with 50 mg/kg plant extract for 21 days following the induction with PCOS. Additionally, the rats in metformin+ extract group were treated with the combination of 50 mg metformin plus plant extract for three weeks. The ovaries were removed and were fixed for tissue processing. The slices were stained by hematoxylin-eosin after clearing and hydration. Follicular count and morphometric changes were evaluated in primordial, primary, pre-antral and antral follicles., Results: The mean diameter of primordial follicle was similar in all groups, but mean diameter of primary follicle decreased in the sham group (145.50± 49.26 µm) compared to metformin (278.76± 156.64 µm), extract (311.70± 147.74 µm) and metformin+ extract groups (265.35± 88.16 µm). The diameter of pre-antral and antral follicles in the sham group were significantly larger than those in the control group, but were not significantly different in all other groups including metformin, extract, and metformin+ extract in comparison with control group (P< 0.05)., Conclusion: In this study, the data has demonstrated that CCT like metformin could improve follicular morphometric disorders in PCOS rats., Competing Interests: All the authors declare that there is no conflict of interest., (Copyright© 2018, Galen Medical Journal.)

Bachground: The inhibitory effects of morphine and the stimulatory influence of kisspeptin signaling have been demonstrated on gonadotropin releasing hormone (GnRH)/luteinizing hormone (LH) release. Hypothalamic kisspeptin is involved in relaying the environmental and metabolic information to reproductive axis. In the present study, the role of kisspeptin/ GPR54 signaling system was investigated on relaying the inhibitory influences of morphine on LH hormone secretion., Materials and Methods: In this experimental study, 55 wistar male rats weighing 230-250 g were sub-grouped in 11 groups (in each group n=5) receiving saline, kisspeptin (1 nmol), peptide234 (P234, 1 nmol), morphine (5 mg/kg), naloxone (2 mg/kg), kisspeptin/P234, morphine/naloxone, kisspeptin/morphine, kisspeptin/naloxone, P234/morphine or P234/naloxone respectively. Blood samples were collected via tail vein. Mean plasma (LH) concentrations and mean relative KiSS1 or GPR54 mRNA levels were determined by radioimmunoassay (RIA) and real time reverse transcriptase-polymerase chain reaction (RT-PCR), respectivwely., Results: Morphine significantly decreased mean plasma LH concentration and mean relative KiSS1 gene expression compared to saline; while it did not significantly decrease mean relative GPR54 gene expression compared to saline. Naloxone significant increased mean LH level and mean relative KiSS1 gene expression compared to saline; while it did not significantly increase mean relative GPR54 gene expression compared to saline. Injections of kisspeptin plus morphine significantly increased mean LH concentration compared to saline or morphine, while simultaneous infusions of them significantly declined mean plasma LH level compared to kisspeptin. In kisspeptin/naloxone group mean plasma LH level was significantly increased compared to saline or naloxone. Co-administration of P234/morphine significantly decreased mean LH concentration compared to saline., Conclusion: Down regulation of KiSS1 gene expression may be partly involved in the mediating the inhibitory effects of morphine on reproductive axis., Competing Interests: The authors declare no conflicts of interest., (Copyright© by Royan Institute. All rights reserved.)

Background: Studies of oxidative status in polycystic ovarian syndrome (PCOS) patients are limited with inconsistent results. The effects of resveratrol as a natural antioxidant on oxidative status in PCOS aren't clear., Objective: This study evaluated effects of resveratrol on oxidative stress in the liver and serum of the PCOS rats., Materials and Methods: Fifteen female Wistar rats (3 wk old) were divided into 3 groups (n=5/each e): Control group, PCO-Control group, and PCO-Resveratrol group. For induction of polycystic ovary phenotype, testosterone enanthate 10 mg/kg was injected for 35 days subcutaneously. Then, resveratrol 10 mg/kg was injected intraperitoneally for 28 days to rats of the PCO-Resveratrol group. Ovarian sections were stained with hematoxylin/eosin. The serum glucose and insulin and the levels of malondialdehyde (MDA) and total antioxidant capacity (TAC) in serum and liver were measured., Results: Control animals showed normal ovarian morphology and PCO-Control animals exhibited cystic follicles. There were no significant differences in liver TAC between groups. The serum MDA (p=0.034), and homeostatic model assessment insulin resistance (HOMA-IR) (p=0.014) levels in PCO-Control rats were higher than the controls. The liver MDA in PCO-Control rats was more than that of controls (p=0.001). The HOMA-IR (p=0.008) and serum MDA (p=0.006) levels in PCO-Control rats were more than those of PCO-Resveratrol rats (p=0.008). In PCO-Resveratrol group, serum TAC was higher than that of PCO-Control group (p=0.022) and liver MDA was more than controls (p=0.01)., Conclusion: Results indicated that the induction of PCOS in rats increased lipid peroxidation and insulin resistance and resveratrol improved these complications., Competing Interests: The authors have no conflict of interest.

Objectives: Some studies suggest that chronic low-grade inflammation is involved in insulin resistance in polycystic ovary syndrome (PCOS). This study assessed possible involvement of alteration in expression of two pro-inflammatory factors, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in adipose tissues of PCOS rats in the impairment of insulin actions. Also, effects of resveratrol as an anti-inflammatory agent were investigated., Materials and Methods: Fifteen female Wistar rats (21 days old) were divided into three groups (n=5): I) Control, II) PCO-model-saline: served as PCOS rats and to induce PCOS, received subcutaneously testosterone enanthate 1 mg/100 g body weight subcutaneously for 35 days, III) PCO-model-resveratrol, after receiving testosterone, received resveratrol 10 mg/kg intraperitoneally for 28 days. The expression of Tnf-α and Il-6 mRNAs in adipose tissues was determined by the qRT-PCR method., Results: The Il-6 mRNA expression in the visceral adipose tissue of PCOS rats was increased in comparison to controls ( P <0.05). Tnf-α and Il-6 mRNA expression in visceral and subcutaneous adipose tissues of polycystic ovarian rats was similar to controls. The expression of Tnf-α mRNA in subcutaneous adipose tissue and Tnf-α and Il-6 mRNAs in the visceral adipose tissue of the PCO-model-resveratrol group were lower than PCOS rats ( P <0.05)., Conclusion: Increased expression of Il-6 mRNA in the visceral adipose tissue of polycystic ovarian rats may be one cause of insulin resistance observed in them and resveratrol as an anti-inflammatory and anti-hyperglycemic agent may decrease the risk of diabetes by reduction of expression of pro-inflammatory cytokines TNF-α and IL-6 in PCOS patients.

Background: Polycystic ovarian syndrome (PCOS) is the most frequent female endocrine disorder that affects 5-10% of women. PCOS is characterized by hyperandrogenism, oligo-/anovulation, and polycystic ovaries. The aim of the present research is to evaluate the expression of steroidogenic acute regulatory protein (StAR) and aromatase (CYP19) mRNA in the ovaries of an estradiol valerate (EV)-induced PCOS rat model, and the effect of treadmill and running wheel (voluntary) exercise on these parameters., Materials and Methods: In this experimental study, we divided adult female Wistar rats that weighed approximately 220 ± 20 g initially into control (n=10) and PCOS (n=30). Subsequently, PCOS group were divided to PCOS, PCOS with treadmill exercise (P-ExT), and PCOS with running wheel exercise (P-ExR) groups (n=10 per group). The expressions of StAR and CYP19 mRNA in the ovaries were determined by quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR). Data were analyzed by one-way ANOVA using SPSS software, version 16. The data were assessed at α=0.05., Results: There was significantly lower mRNA expression of CYP19 in the EV-induced PCOS, running wheel and treadmill exercise rats compared to the control group (P<0.001). Treadmill exercise (P=0.972) and running wheel exercise (P=0.839) had no significant effects on CYP19 mRNA expression compared to the PCOS group. mRNA expression of StAR in the ovaries of the PCOS group indicated an increasing trend compared to the control group, however this was not statistically significant (P=0.810). We observed that 8 weeks of running wheel and treadmill exercises could not statistically decrease StAR mRNA expression compared to the PCOS group (P=0.632)., Conclusion: EV-induced PCOS in rats decreased CYP19 mRNA expression, but had no effect on StAR mRNA expression. We demonstrated that running wheel and moderate treadmill exercise could not modify CYP19 and StAR mRNA expressions., Competing Interests: The authors declare that there is no conflict of interest., (Copyright© by Royan Institute. All rights reserved.)

Hypogonadotropic hypogonadism (HH) is a form of hypogonadism which also known as secondary or central hypogonadism. Congenital HH can occur due to defect in gonadotropin releasing hormone (GnRH) neurons, upstream regulators of GnRH neurons or pituitary gonadotropic cells. Testosterone or gonadotropins therapy are widely used to treat HH patients, however both have undesirable effects and GnRH treatment for HH patients is time and cost consuming. Direct delivery of therapeutics to the brain via the nasal route is located in the center of attention during the last decade and trial application of intranasal oxytocin as a method of enhancing social interactions are reported. It has been delineated that oxytocin stimulates GnRH release from the rat hypothalamic explants and intranasal applied oxytocin up-regulates GnRH expression in the male rat hypothalamus. Therefore application of intranasal oxytocin might be a new strategy to cure HH patients., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Citrullus colocynthis (CCT) is used as the anti-diabetic and antioxidant agent. Polycystic ovarian syndrome (PCOS) is a reproductive disorder which level of gonadotropins and sexual hormones are imbalanced., Objective: We evaluated the effect of CCT hydro-alcoholic extract on hormonal and folliculogenesis process in estradiol valerate-induced PCOs rats' model., Materials and Methods: 40 female adult Wistar rats divided into five groups (n=8each: Group I (control) only injected by sesame oil as estradiol valerate solvent, group II (Sham) was orally received normal saline after estradiol valerate- induced polycystic ovarian syndrome (4 mg/rat estradiol valerate, intramuscularly), and three experimental groups, that after induction of PCOS within 60 days, received orally 50 mg/kg CCT extract (group III), 50mg/kg metformin (group IV), and CCT extract+ metformin (group V) for 20 days. The serum concentration level of luteinizing, testosterone and follicle stimulating hormones were measured using ELISA method and the serum concentration level of glucose were measured using the oxidative method (glucose meter). Histological study of ovary tissue carried out by hematoxylin-eosin staining., Results: There was a significant reduction in luteinizing hormone and testosterone in III-V groups compared to Sham group, whereas follicle stimulating hormone in III-V groups was not significantly changed in comparison with Sham group. Histological investigations showed a significant increase in number of preantral and antral follicles and corpus luteum in the experimental groups compared to group II., Conclusion: Marked improvement in hormonal and histological symptoms of PCOS may be due to CCT effects hence, CCT can potentially be considered as an effective drug for treatment of PCOS., Competing Interests: The authors have no financial or nonfinancial conflicts of interest.

The last decade has witnessed a surge in studies on the clinical applications of intranasal oxytocin as a method of enhancing social interaction. However, the molecular and cellular mechanisms underlying its function are not completely understood. Since oxytocin is involved in the regulation of hypothalamic-pituitary-gonadal axis by affecting the gonadotropin-releasing hormone (GNRH) system, the present study addressed whether intranasal application of oxytocin has a role in affecting GNRH expression in the male rat hypothalamus. In addition, we assessed expression of two excitatory (kisspeptin and neurokinin B) and two inhibitory (dynorphin and RFamide-related peptide-3) neuropeptides upstream of GNRH neurons as a possible route to relay oxytocin information. Here, adult male rats received 20, 40, or 80 μg oxytocin intranasally once a day for 10 consecutive days, and then, the posterior (PH) and anterior hypothalamus (AH) dissected for evaluation of target genes. Using qRT-PCR, we found that oxytocin treatment increased Gnrh mRNA levels in both the PH and AH. In addition, oxytocin at its highest dose increased kisspeptin expression in the AH by around 400%, whereas treatments, dose dependently decreased kisspeptin mRNA in the PH. The expression of neurokinin B was increased from the basal levels following the intervention. Furthermore, although intranasal-applied oxytocin decreased hypothalamic RFamide-related peptide-3 mRNA level, the dynorphin mRNA was not affected. These observations are consistent with the hypothesis that applications of intranasal oxytocin can affect the GNRH system.