• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6215-6220
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• 2013

Kisspeptins (KPs) encoded by the KiSS-1 gene are C-terminally amidated peptide products, including KP-10, KP-13, KP-14 and KP-54, which are endogenous agonists for the G-protein coupled receptor-54 (GPR54). Functional analyses have demonstrated fundamental roles of KiSS-1 in whole body homeostasis including sexual differentiation of brain, action on sex steroids and metabolic regulation of fertility essential for human puberty and maintenance of adult reproduction. In addition, intensive recent investigations have provided substantial evidence suggesting roles of Kisspeptin signalling via its receptor GPR54 in the suppression of metastasis with a variety of cancers. The present review highlights the latest studies regarding the role of Kisspeptins and the KiSS-1 gene in tumor progression and also suggests targeting the KiSS-1/GPR54 system may represent a novel therapeutic approach for cancers. Further investigations are essential to elucidate the complex pathways regulated by the Kisspeptins and how these pathways might be involved in the suppression of metastasis across a range of cancers.

• 한국발생생물학회지:발생과생식
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• 제26권3호
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• pp.107-115
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• 2022

Kisspeptins, products of KISS1 gene, are ligands of the G-protein coupled receptor (GPR54), and the kisspeptin-GPR54 signaling has an important role as an upstream regulator of gonadotropin releasing hormone (GnRH) neurons. Interestingly, extrahypothalamic expressions of kisspeptin/GPR-54 in gonads have been found in primates and experimental rodents such as rats and mice. Hamsters, another potent experimental rodent, also have a kisspeptin-GPR54 system in their ovaries. The presence of testicular kisspeptin-GPR54 system, however, remains to be solved. The present study was undertaken to determine whether the kisspeptin is expressed in hamster testis. To do this, reverse transcription-polymerase chain reactions (RT-PCRs) and immunohistochemistry (IHC) were employed. After the nest PCR, two cDNA products (320 and 280 bp, respectively) were detected by 3% agarose gel electrophoresis, and sequencing analysis revealed that the 320 bp product was correctly amplified from hamster kisspeptin cDNA. Modest immunoreactive (IR) kisspeptins were detected in Leydig-interstitial cells, and the weak signals were detected in germ cells, mostly in round spermatids and residual bodies of elongated spermatids. In the present study, we found the kisspeptin expression in the testis of Syrian hamster. Further studies on the local role(s) of testicular kisspeptin are expected for a better understanding the physiology of hamster testis, including photoperiodic gonadal regression specifically occurred in hamster gonads.

• 한국발생생물학회지:발생과생식
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• 제9권1호
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• pp.1-5
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• 2005

시상하부-뇌하수체-생식소(HPG) 호르몬 축은 유아기와 아동기에는 작동하지 않다가 사춘기 개시 직전에 활성화되는 흥분성 및 억제성 신호들의 복잡한 중추성 조절 네트워크에 의해 조절된다. 최근 주목받고 있는 kisspeptin은 KiSS-1 유전자의 펩타이드 산물로, 최초 orphan receptor로 클로닝된 G protein-coupled receptor 54(GPR54)의 내인성 리간드이다. KiSS-l은 본래 종양전이억제 유전자로 알려졌으나, 최근의 연구들은 KiSS-1/GPR54 시스템이 생식계의 주요한 조절자임을 시사하고 있다. 비록 생식 관련 호르몬 분비의 신경내분비적 조절에서 KiSS-1/GPR54 시스템의 정확한 역할은 아직 자세히 모르지만, 이 시스템은 생식호르몬 축에서의 일차적인 연결 고리일 수 있다. 중추적(icv) 또는 말초적(sc 또는 ip)으로 kisspeptin을 주사할 경우 시상하부-뇌하수체-생식소 축이 자극되어 혈중 LH 수준이 증가함이 설치류, 양, 원숭이 그리고 인간을 대상으로 한 실험들에서 관찰되었다. 이러한 kisspeptin의 효과는 시상하부 GnRH 신경계를 경유하여 나타나는 것으로 보이지만, 뇌하수체 전엽에 직접 작용할 수도 있다. GPR54 녹아웃 생쥐에서는 사춘기 개시의 소실과 생식소자극호르몬 저하성 생식소 기능저하증(hypogonadotropic hypogonadism, HH)이 나타났다. 따라서 kisspeptin 주사는 인간의 생식계 이상을 치료하기 위한 HPG 축을 활성화시키는 치료에 응용할 수 있을 것이다.

• Clinical and Experimental Reproductive Medicine
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• 제40권4호
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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.