• Development and Reproduction
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• v.16 no.1
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• pp.31-38
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• 2012

Kisspeptin has been implicated in the process of puberty onset in various animal groups. This peptide is encoded by a gene, Kiss1 in avian and mammalian species. Contrary to these higher vertebrates, however, fish appeared to have another gene, Kiss2 that also codes for the precursor peptide of kisspeptin. To figure out biological significance of this gene during the puberty onset in fish, the expression profile of Kiss2 gene was investigated in the brain of Nile tilapia together with genes of GPR54, GnRH receptorI (rGnRHI) and GTH subunits ($LH{\beta}$ and $FSH{\beta}$). Expression of Kiss2 mRNA significantly increased at 2 weeks post hatch (wph) and 13 wph ($P$<0.05). This increase coincided with the increases of GPR54 and rGnRH I gene expression. Detection of $LH{\beta}$ and $FSH{\beta}$ subunit gene expression was possible later than 13 wph, indicating the activation of gonadotrophs in the pituitary. Data obtained from this study strongly suggest that, in addition to Kiss1 gene, Kiss2 gene is deeply associated with the onset of puberty by the activation of hypothalamus pituitary gonadal axis in Nile tilapia.

• Clinical and Experimental Pediatrics
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• v.65 no.4
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• pp.172-181
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• 2022

Pubertal onset is known to result from reactivation of the hypothalamic-pituitary-gonadal (HPG) axis, which is controlled by complex interactions of genetic and nongenetic factors. Most cases of precocious puberty (PP) are diagnosed as central PP (CPP), defined as premature activation of the HPG axis. The cause of CPP in most girls is not identifiable and, thus, referred to as idiopathic CPP (ICPP), whereas boys are more likely to have an organic lesion in the brain. ICPP has a genetic background, as supported by studies showing that maternal age at menarche is associated with pubertal timing in their offspring. A gain of expression in the kisspeptin gene (KISS1), gain-of-function mutation in the kisspeptin receptor gene (KISS1R), loss-of-function mutation in makorin ring finger protein 3 (MKRN3), and loss-of-function mutations in the delta-like homolog 1 gene (DLK1) have been associated with ICPP. Other genes, such as gamma-aminobutyric acid receptor subunit alpha-1 (GABRA1), lin-28 homolog B (LIN28B), neuropeptide Y (NPYR), tachykinin 3 (TAC3), and tachykinin receptor 3 (TACR3), have been implicated in the progression of ICPP, although their relationships require elucidation. Environmental and socioeconomic factors may also be correlated with ICPP. In the progression of CPP, epigenetic factors such as DNA methylation, histone posttranslational modifications, and non-coding ribonucleic acids may mediate the relationship between genetic and environmental factors. CPP is correlated with short- and long-term adverse health outcomes, which forms the rationale for research focusing on understanding its genetic and nongenetic factors.

• Asian-Australasian Journal of Animal Sciences
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• v.31 no.6
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• pp.835-841
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• 2018

Objective: The aim of this study was to investigate the reversibility and safety of KISS1 metastasis suppressor (KISS1) gene vaccine in immunocastration. Methods: Six eight-week old ram lambs were randomly divided into vaccinated and control groups. The vaccine (1 mg/ram lamb) was injected at weeks 0, 3, and 6 of the study. Blood samples were collected from the jugular vein before primary immunization and at weeks 2, 4, 6, 10, 14, 22, and 30 after primary immunization. All ram lambs were slaughtered at 38 weeks of age, and samples were collected. Results: The specific anti-KISS1 antibody titers in vaccinated animals were significantly higher and the serum testosterone level was significantly lower than those in the control groups from week 4 to 14 after primary immunization (p<0.05). No significant difference was observed at weeks 22 and 30 after the primary immunization. Similar results were also found for scrotal circumference, testicular weight, length, breadth, and spermatogenesis in seminiferous tubules in week 30 after primary immunization. KS (KISS1-hepatitis B surface antigen S) fusion fragment of KISS1 gene vaccine was not detected in host cell genomic DNA of 9 tissues of the vaccinated ram lambs by polymerase chain reaction. Conclusion: The effects of KISS1 gene vaccine in immunocastration were reversible and no integration events were recorded.

• Journal of Marine Life Science
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• v.1 no.1
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• pp.41-49
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• 2016

Kisspeptin (Kiss) and its cognate receptor, kisspeptin receptor (KissR; G protein coupled receptor 54, GPR54), have recently been recognized as potent regulators of reproduction in teleosts. Additionally, leptin plays an important role in energy homeostasis and reproductive function in teleosts. The purpose of this study was to examine differences in the concentration of the hormones of the Kiss/KissR system and leptin and the expression of their underlying genes, all of which are involved in the sexual maturation of female goldfish, Carassius auratus, following treatment with Kiss. The expression levels of KissR increased after the Kiss injection. Furthermore, the peptide hormone leptin also increased after the injection (in vivo and in vitro). Additionally, the expression of GnRH and GTHs (GTHα, FSHβ, and LHβ) increased in the brain and pituitary (in vitro and in vitro). These results support the hypothesis that Kiss plays important roles in the direct regulation of the hypothalamus-pituitary-gonad axis and leptin in goldfish. Therefore, we suggest that Kiss system gene expression is correlated with energy balance and reproduction.

• Clinical and Experimental Reproductive Medicine
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• v.40 no.4
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• pp.155-162
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• 2013

Objective: Stress is known to be an inhibitor of the reproductive hypothalamic-pituitary-gonadal (HPG) axis. However, the neural and molecular connections between stress and reproduction are not yet understood. It is well established that in both humans and rodents, kisspeptin (encoded by the kiss1 gene) is a strong stimulator of the HPG axis. In the present study we hypothesized that endocannabinoids, an important neuromodulatory system in the brain, can act on the HPG axis at the level of kiss1 expression to inhibit reproductive function under stress. Methods: Adult male Wistar rats were unilaterally implanted with an intracerebroventricular cannula. Afterwards, the animals were exposed to immobilization stress, with or without the presence of the cannabinoid CB1 receptor antagonist AM251 (1 ${\mu}g/rat$). Blood samples were collected through a retro-orbital plexus puncture before and after stress. Five hours after the stress, brain tissue was collected for reverse transcriptase-quantitative polymerase chain reaction measurements of kiss1 mRNA. Results: Immobilization stress (1 hour) resulted in a decrease in the serum luteinizing hormone concentration. Additionally, kiss1 gene expression was decreased in key hypothalamic nuclei that regulate gonadotrophin secretion, the medial preoptic area (mPOA), and to some extent the arcuate nucleus (ARC). A single central administration of AM251 was effective in blocking these inhibitory responses. Conclusion: These findings suggest that endocannabinoids mediate, at least in part, immobilization stress-induced inhibition of the reproductive system. Our data suggest that the connection between immobilization stress and the HPG axis is kiss1 expression in the mPOA rather than the ARC.

• Ocean and Polar Research
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• v.38 no.1
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• pp.81-88
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• 2016

In many fish species, including Nile tilapia (Oreochromis niloticus), gonadal development occurs at the expense of stored energy and nutrients. Therefore, reproductive systems are inhibited by limited food supply. It has been well established that reproductive function is highly sensitive to both metabolic status and energy balance. Nothing is known about the possible mediated connection between energy balance and reproduction. Kisspeptin, a neuropeptide product of the Kiss gene has emerged as an essential gatekeeper of reproduction and may be possibly be linked to energy balance and reproduction in non-mammalians. Thus, in this study, the effect of fasting (10 days) on the expression of kisspeptin and the gonadotropin-releasing hormone (GnRH) gene were assessed in Nile tilapia (male and female) using qRT-PCR. In addition, plasma levels of estradiol-$17{\beta}$ ($E_2$) and 11-ketotestosterone (11-KT) in adult tilapia were measured by ELISA. In male tilapia, fasting reduced Kiss2 and GnRH I mRNA expression in the brain and 11-KT level in comparison with the fed tilapia (p < 0.05). In females, however, there were no significant differences in GnRH I mRNA expression and $E_2$ between fish subjected to fasting and those fed (p > 0.05). These data indicate the impact of nutritional states on kisspeptin as a potential regulatory mechanism for the control of reproduction in male Nile tilapia.

• Clinical and Experimental Pediatrics
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• v.55 no.1
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• pp.6-10
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• 2012

Human puberty is a complex, coordinated biological process with multiple levels of regulations. The timing of puberty varies greatly in children and is influenced by both environmental and genetic factors. The key genes of pubertal onset, $KISS1$, $GPR54$, $GNRH1$ and $GNRHR$, may be major causal factors underlying gonadotropin-releasing hormone-dependent precocious puberty (GDPP). Two gain-of-function mutations in $KISS1$ and $GPR54$ have been identified recently as genetic causes of GDPP. $GNRH1$ and $GNRHR$ are also gene candidates for GDPP; however no mutations have been identified in these genes. Presently potential genetic causes like $LIN28B$ continues to appear; many areas of research await exploration in this context. In this review, I focus primarily on the genetic causes of GDPP.

• The Journal of the Korea Contents Association
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• v.17 no.7
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• pp.648-663
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• 2017

To verify the association between GSTM1/GSTT1 gene polymorphisms and susceptibility to autoimmune diseases in Asian population. 18 published reports cited in EMBASE, Google, KISS, MEDLINE and PubMed up to December 2015 were collected for a meta-analysis. The GSTM1/GSTT1 polymorphism for null and present type were analysed separately. The significant association was found between the GST polymorphism and autoimmune diseases in an overall population (GSTM1, OR=1.334, 95% CI=1.137-1.567, p=0.000; GSTT1, OR=1.212, 95% CI=1.012-1.452, p=0.037). Asian population showed the significant association of GSTM1 in the autoimmune diseases, especially vitiligo and atopic dermatitis but non-significant association of GSTT1 in RA and SLE. The GSTM1 null and the GSTT1 present type showed the association with autoimmune diseases in Asian population. The null type frequency of the combination of GSTM1-GSTT1 polymorphism in autoimmune diseases in Asian population was higher than that of the control group. This result indicated that null type of GSTM1-GSTT1 combination can be a risk factor of autoimmune diseases in Asian population.

• Development and Reproduction
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• v.20 no.1
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• pp.51-61
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• 2016

Neurokinin B (NKB) and neurokinin B related peptide (NKBRP) belong to tachykinin peptide family. They act as a neurotransmitter and/or neuromodulator. Mutation of NKB and/or its cognate receptor, NK3R resulted in hypogonadotropic hypogonadism in mammals, implying a strong involvement of NKB/NK3R system in controlling mammalian reproduction. Teleosts possess NKBRP as well as NKB, but their roles in fish reproduction need to be clarified. In this study, NKB and NKBRP coding gene (tac3) was cloned from Nile tilapia and sequenced. Based on the sequence, Nile tilapia NKB and NKBRP peptide were synthesized and their biological potencies were tested in vitro pituitary culture. The synthetic NKBRP showed direct inhibitory effect on the expression of GTH subunits at the pituitary level. This inhibitory effect was confirmed in vivo by means of intraperitoneal (ip) injection of synthetic NKB and NKBRP to mature female tilapia (20 pmol/g body weight [BW]). Both NKB and NKBRP had no effect on the plasma level of sex steroids, E2 and 11-KT. However, NKBRP caused declines of expression level of GnRH I, Kiss2 and tac3 mRNAs in the brain while NKB seemed to have no distinct effect. These results indicate some inhibitory roles of NKBRP in reproduction of mature female Nile tilapia, although their exact functions are not clear at the moment.

• Development and Reproduction
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• v.24 no.3
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• pp.149-158
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• 2020

Kisspeptin, expressed mainly in the hypothalamus, stimulates gonadotropin-releasing hormone neurons to facilitate reproduction. In some model animals, the kisspeptin is also expressed in the pituitary. Recently, a pathway has been suggested in which kisspeptin acts directly on the pituitary to secretion of gonadotropin in mammals. In the present study, pituitaries of the Nile tilapia (Oreochromis niloticus) were cultured at different concentrations of kisspeptin-10 (Kp-10, FNYNPLSLRF) for 3 hours to observe the effect of kisspeptin on the expression of follicle-stimulating hormone β subunit (fshβ) gene and luteinizing hormone β subunit (lhβ) gene. Pituitary tissues were cultured with 0.1 μM of Kp-10, luteinizing hormone releasing hormone (LHRH), or LHRH+Kp-10 for 3, 6, 12, and 24 hours to investigate changes in the expression of fshβ and lhβ mRNA. Pituitaries cultured with high concentration of Kp-10 more than 0.1 μM for 3 hours exhibited a significant increase of fshβ mRNA expression, but not lhβ mRNA. The expression of both fshβ and lhβ mRNA increased after 6 hours in 0.1 μM of Kp-10 medium in comparison with that in the control medium. Tissues cultured in the LHRH medium however exhibited increased expression of both genes not only at 6 but also 12 hours. There were no significant differences of fshβ and lhβ gene expression in tissues cultured with LHRH+KP-10 medium compared with the control. These results suggested that although kisspeptin plays an important role in fshβ and lhβ expression in the pituitary of Nile tilapia, its action is far more complicated than expected.