Kisspeptin signaling at the gonadotropin-releasing hormone (GnRH) neuron is now relatively well characterized and established as being critical for the neural control of fertility. However, kisspeptin fibers and the kisspeptin receptor (KISS1R) are detected throughout the brain suggesting that kisspeptin is involved in regulating the activity of multiple neuronal circuits. We provide here a review of kisspeptin actions on neuronal populations throughout the brain including the magnocellular oxytocin and vasopressin neurons, and cells within the arcuate nucleus, hippocampus, and amygdala. The actions of kisspeptin in these brain regions are compared to its effects upon GnRH neurons. Two major themes arise from this analysis. First, it is apparent that kisspeptin signaling through KISS1R at the GnRH neuron is a unique, extremely potent form or neurotransmission whereas kisspeptin actions through KISS1R in other brain regions exhibit neuromodulatory actions typical of other neuropeptides. Second, it is becoming increasingly likely that kisspeptin acts as a neuromodulator not only through KISS1R but also through other RFamide receptors such as the neuropeptide FF receptors (NPFFRs). We suggest likely locations of kisspeptin signaling through NPFFRs but note that only limited tools are presently available for examining kisspeptin cross-signaling within the RFamide family of neuropeptides.

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• Role of the histone variant H2A.Z.1 in memory, transcription, and alternative splicing is mediated by lysine modification
  Anas Reda, Luca A. Hategan, Timothy A. B. McLean, Samantha D. Creighton, Jian Qi Luo, Sean En Si Chen, Shan Hua, Stephen Winston, Isaiah Reeves, Aditya Padmanabhan, Tarkan A. Dahi, Firyal Ramzan, Mark A. Brimble, Patrick J. Murphy, Brandon J. Walters, Gil
  Neuropsychopharmacology.2024;[Epub]     CrossRef
• System-wide mapping of peptide-GPCR interactions in C. elegans
  Isabel Beets, Sven Zels, Elke Vandewyer, Jonas Demeulemeester, Jelle Caers, Esra Baytemur, Amy Courtney, Luca Golinelli, İlayda Hasakioğulları, William R. Schafer, Petra E. Vértes, Olivier Mirabeau, Liliane Schoofs
  Cell Reports.2023; 42(9): 113058.     CrossRef
• Impose of KNDy/GnRH neural circuit in PCOS, ageing, cancer and Alzheimer’s disease: StAR actions in prevention of neuroendocrine dysfunction
  Siva Prasad Panda, Adarsh Kesharwani, Gaurav Deep Singh, DSNBK Prasanth, Bhaskara Raju Vatchavai, P.V. Kamala Kumari, Sunil Kumar Panda, Sarada Prasanna Mallick
  Ageing Research Reviews.2023; 92: 102086.     CrossRef
• Gallium-68-Labeled KISS1-54 Peptide for Mapping KISS1 Receptor via PET: Initial Evaluation in Human Tumor Cell Lines and in Tumor-Bearing Mice
  Ina Israel, Gabriele Riehl, Elke Butt, Andreas K. Buck, Samuel Samnick
  Pharmaceuticals.2023; 17(1): 44.     CrossRef
• Kisspeptin-13 prevented the electrophysiological alterations induced by amyloid-beta pathology in rat: Possible involvement of stromal interaction molecules and pCREB
  Shima Ebrahimi Khonacha, Seyed Hamidreza Mirbehbahani, Mona Rahdar, Shima Davoudi, Mehdi Borjkhani, Fariba Khodagholi, Fereshteh Motamedi, Mahyar Janahmadi
  Brain Research Bulletin.2022; 184: 13.     CrossRef
• Sexual Dimorphism in Kisspeptin Signaling
  Eun Bee Lee, Iman Dilower, Courtney A. Marsh, Michael W. Wolfe, Saeed Masumi, Sameer Upadhyaya, Mohammad A. Karim Rumi
  Cells.2022; 11(7): 1146.     CrossRef
• Estradiol and progesterone-induced lordosis behavior is modulated by both the Kisspeptin receptor and melanin-concentrating hormone in estradiol benzoate-primed rats
  Oscar González-Flores, James G. Pfaus, Ailyn Luna-Hernández, Omar Montes-Narváez, Raymundo Domínguez-Ordóñez, Miriam B. Tecamachaltzi-Silvarán, Marcos García-Juárez
  Hormones and Behavior.2022; 146: 105257.     CrossRef
• Targeting KNDy neurons to control GnRH pulses
  Stephanie Constantin
  Current Opinion in Pharmacology.2022; 67: 102316.     CrossRef
• The ameliorative effects of Lactobacillus coagulans and Lactobacillus casei probiotics on CCl4‐induced testicular toxicity based on biochemical, histological and molecular analyses in rat
  Zahra Keshtmand, Mohsen Akbaribazm, Yasin Bagheri, Reyhaneh Oliaei
  Andrologia.2021;[Epub]     CrossRef
• Nitric oxide resets kisspeptin-excited GnRH neurons via PIP2 replenishment
  Stephanie Constantin, Daniel Reynolds, Andrew Oh, Katherine Pizano, Susan Wray
  Proceedings of the National Academy of Sciences.2021;[Epub]     CrossRef
• Expression analysis of neuropeptide FF receptors on neuroendocrine-related neurons in the rat brain using highly sensitive in situ hybridization
  Shimpei Higo, Moeko Kanaya, Hitoshi Ozawa
  Histochemistry and Cell Biology.2021; 155(4): 465.     CrossRef
• Timing the Juvenile-Adult Neurohormonal Transition: Functions and Evolution
  Celia G. Barredo, Beatriz Gil-Marti, Derya Deveci, Nuria M. Romero, Francisco A. Martin
  Frontiers in Endocrinology.2021;[Epub]     CrossRef
• Kisspeptin-54 attenuates oxidative stress and neuronal apoptosis in early brain injury after subarachnoid hemorrhage in rats via GPR54/ARRB2/AKT/GSK3β signaling pathway
  Yi Huang, Yong Guo, Lei Huang, Yuanjian Fang, Dujuan Li, Rui Liu, Qin Lu, Reng Ren, Lihui Tang, Lifei Lian, Yongmei Hu, Jiping Tang, Gao Chen, John H. Zhang
  Free Radical Biology and Medicine.2021; 171: 99.     CrossRef
• Conditioned place preference of kisspeptin-10
  Ilia Yu. Tissen, Polina A. Chepik, Andrei A. Lebedev, Leila A. Magarramova, Eugenii R. Bychkov, Petr D. Shabanov
  Reviews on Clinical Pharmacology and Drug Therapy.2021; 19(1): 47.     CrossRef
• Expression of type one cannabinoid receptor in different subpopulation of kisspeptin neurons and kisspeptin afferents to GnRH neurons in female mice
  Tamás Wilheim, Krisztina Nagy, Mahendravarman Mohanraj, Kamil Ziarniak, Masahiko Watanabe, Joanna Sliwowska, Imre Kalló
  Brain Structure and Function.2021; 226(7): 2387.     CrossRef
• Dopamine D2 Receptor Antagonist Alters the Testosterone Release and Kisspeptin/GPR54 Signaling in Food-Restricted Rats
  Khatereh Nourmohammadi, Farrin Babaei-Balderlou, Seyyed Meysam Abtahi-Foroushani
  Iranian Journal of Science and Technology, Transactions A: Science.2021; 45(6): 1879.     CrossRef
• Astrocytic Hydrogen Sulfide Regulates Supraoptic Cellular Activity in the Adaptive Response of Lactating Rats to Chronic Social Stress
  Dongyang Li, Haitao Liu, Hongyang Wang, Shuwei Jia, Xiaoran Wang, Shuo Ling, Guichuan Chen, Xiaoyu Liu, Yu-Feng Wang
  ASN Neuro.2021; 13: 175909142110430.     CrossRef
• Experimental characterization of a biosensor based on a tapered optical fiber for kisspeptin detection
  K. González-León, G. Beltrán-Pérez, S. Muñoz-Aguirre, V. López -Gayou, J. Castillo-Mixcoatl, V. Alatriste, R. Delgado-Macuil
  Applied Optics.2020; 59(13): D131.     CrossRef
• Cloning, characterisation and expression profile of kisspeptin1 and the kisspeptin1 receptor in the hypothalamic–pituitary–ovarian axis of Chinese alligator Alligator sinensis during the reproductive cycle
  Ruidong Zhang, Haitao Nie, Shulong Duan, Peng Yan, Ali Izaz, Renping Wang, Yongkang Zhou, Xiaobing Wu
  Reproduction, Fertility and Development.2020; 32(8): 792.     CrossRef
• Multiple failures in the lutenising hormone surge generating system in GABAB1KO female mice
  Noelia P. Di Giorgio, Marianne Bizzozzero Hiriart, Pablo N. Surkin, Paula V. López, Nadia S. Bourguignon, Verónica B. Dorfman, Bernhard Bettler, Carlos Libertun, Victoria Lux‐Lantos
  Journal of Neuroendocrinology.2019;[Epub]     CrossRef
• Vasopressin regulates hypothalamic GnRH synthesis: Histomorphological evidence in hypothalamus and biological effects in GT1-7 cells
  Zhu Zhu, Xiaozhen Zhao, Feng Huang, Feng Wang, Wei Wang
  Life Sciences.2019; 227: 166.     CrossRef
• The kisspeptin derivative kissorphin reduces the acquisition, expression, and reinstatement of ethanol-induced conditioned place preference in rats
  Ewa Gibula-Tarlowska, Pawel Grochecki, Jerzy Silberring, Jolanta H. Kotlinska
  Alcohol.2019; 81: 11.     CrossRef
• Unraveling the connection between GABA and kisspeptin in the control of reproduction
  Noelia P Di Giorgio, Marianne Bizzozzero-Hiriart, Carlos Libertun, Victoria Lux-Lantos
  Reproduction.2019; 157(6): R225.     CrossRef
• Region-specific changes in brain kisspeptin receptor expression during estrogen depletion and the estrous cycle
  Saeko Ozaki, Shimpei Higo, Kinuyo Iwata, Hidehisa Saeki, Hitoshi Ozawa
  Histochemistry and Cell Biology.2019; 152(1): 25.     CrossRef
• The long and the short of it – a perspective on peptidergic regulation of circuits and behaviour
  Gáspár Jékely, Sarah Melzer, Isabel Beets, Ilona C. Grunwald Kadow, Joris Koene, Sara Haddad, Lindy Holden-Dye
  Journal of Experimental Biology.2018;[Epub]     CrossRef
• Biological Significance of Kisspeptin–Kiss 1 Receptor Signaling in the Habenula of Teleost Species
  Satoshi Ogawa, Ishwar S. Parhar
  Frontiers in Endocrinology.2018;[Epub]     CrossRef
• Analysis of gonadotrophin‐releasing hormone‐1 and kisspeptin neuronal systems in the nonphotoregulated seasonally breeding eastern rock elephant‐shrew (Elephantulus myurus)
  Katarina Medger, Nigel C. Bennett, Christian T. Chimimba, Maria K. Oosthuizen, Jens D. Mikkelsen, Clive W. Coen
  Journal of Comparative Neurology.2018; 526(15): 2388.     CrossRef
• Altered aspects of anxiety-related behavior in kisspeptin receptor-deleted male mice
  Sarah Delmas, Robert Porteous, Dave H. Bergin, Allan E. Herbison
  Scientific Reports.2018;[Epub]     CrossRef
• Effect of long-term treatment with classical neuroleptics on NPQ/spexin, kisspeptin and POMC mRNA expression in the male rat amygdala
  Artur Pałasz, Marcelina Pałka, Łukasz Filipczyk, Itiana Castro Menezes, Ewa Rojczyk, John J. Worthington, Aneta Piwowarczyk-Nowak, Marek Krzystanek, Ryszard Wiaderkiewicz
  Journal of Neural Transmission.2018; 125(7): 1099.     CrossRef
• Integrative neurohumoural regulation of oxytocin neurone activity in pregnancy and lactation
  R. A. Augustine, A. J. Seymour, R. E. Campbell, D. R. Grattan, C. H. Brown
  Journal of Neuroendocrinology.2018;[Epub]     CrossRef
• Towards new strategies to manage livestock reproduction using kisspeptin analogs
  M. Beltramo, C. Decourt
  Theriogenology.2018; 112: 2.     CrossRef
• キスペプチン神経系機能における脊椎動物間での多様性と普遍性
  
  Comparative Endocrinology.2018; 44(163): 15.     CrossRef
• Articles inEndocrinology and Metabolismin 2016
  Won-Young Lee
  Endocrinology and Metabolism.2017; 32(1): 62.     CrossRef
• Kisspeptin as a promising oocyte maturation trigger for in vitro fertilisation in humans
  Miro Kasum, Daniela Franulić, Ermin Čehić, Slavko Orešković, Albert Lila, Emina Ejubović
  Gynecological Endocrinology.2017; 33(8): 583.     CrossRef
• The association of a probiotic with a prebiotic (Flortec, Bracco) to improve the quality/quantity of spermatozoa in infertile patients with idiopathic oligoasthenoteratospermia: a pilot study
  C. Maretti, G. Cavallini
  Andrology.2017; 5(3): 439.     CrossRef
• Cyclic ADP-Ribose and Heat Regulate Oxytocin Release via CD38 and TRPM2 in the Hypothalamus during Social or Psychological Stress in Mice
  Jing Zhong, Sarwat Amina, Mingkun Liang, Shirin Akther, Teruko Yuhi, Tomoko Nishimura, Chiharu Tsuji, Takahiro Tsuji, Hong-Xiang Liu, Minako Hashii, Kazumi Furuhara, Shigeru Yokoyama, Yasuhiko Yamamoto, Hiroshi Okamoto, Yong Juan Zhao, Hon Cheung Lee, Mak
  Frontiers in Neuroscience.2016;[Epub]     CrossRef
• Role of the Kiss1/Kiss1r system in the regulation of pituitary cell function
  Manuel D. Gahete, Mari C. Vázquez-Borrego, Antonio J. Martínez-Fuentes, Manuel Tena-Sempere, Justo P. Castaño, Raúl M. Luque
  Molecular and Cellular Endocrinology.2016; 438: 100.     CrossRef