The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
Discovery of Potent Kisspeptin Antagonists Delineate Physiological Mechanisms of Gonadotropin Regulation
Open accessAbstract
Neurons that produce gonadotropin-releasing hormone (GnRH) are the final common pathway by which the brain regulates reproduction. GnRH neurons are regulated by an afferent network of kisspeptin-producing neurons. Kisspeptin binds to its cognate receptor on GnRH neurons and stimulates their activity, which in turn provides an obligatory signal for GnRH secretion, thus gating down-stream events supporting reproduction. We have developed kisspeptin antagonists to facilitate the direct determination of the role of kisspeptin neurons in the neuroendocrine regulation of reproduction. In vitro and in vivo studies of analogues of kisspeptin-10 with amino substitutions have identified several potent and specific antagonists. A selected antagonist was shown to inhibit the firing of GnRH neurons in the brain of the mouse and to reduce pulsatile GnRH secretion in female pubertal monkeys; the later supporting a key role of kisspeptin in puberty onset. This analog also inhibited the kisspeptin-induced release of luteinizing hormone (LH) in rats and mice and blocked the postcastration rise in LH in sheep, rats, and mice, suggesting that kisspeptin neurons mediate the negative feedback effect of sex steroids on gonadotropin secretion in mammals. The development of kisspeptin antagonists provides a valuable tool for investigating the physiological and pathophysiological roles of kisspeptin in the regulation of reproduction and could offer a unique therapeutic agent for treating hormone-dependent disorders of reproduction, including precocious puberty, endometriosis, and metastatic prostate cancer.
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Citations
Cites
The GPR54 Gene as a Regulator of Puberty
Seminara, S. B., Messager, S., Chatzidaki, E. E., Thresher, R. R., Acierno, J. S., Shagoury, J. K., Bo-Abbas, Y., Kuohung, W., Schwinof, K. M., Hendrick, A. G., et al. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa035322 · Cited by 2,557
Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54
de Roux, N., Genin, E., Carel, J.-C., Matsuda, F., Chaussain, J.-L., & Milgrom, E. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1834399100 · Cited by 2,431 · cited 1×
“A key candidate transducer emerged in 2003 through genetically-linked mutations in a G protein-coupled receptor (gpr-54) (de Roux et al., 2003; Seminara et al., 2003).”
Kotani, M., Detheux, M., Vandenbogaerde, A., Communi, D., Vanderwinden, J.-M., Le Poul, E., Brézillon, S., Tyldesley, R., Suarez-Huerta, N., Vandeput, F., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m104847200 · Cited by 1,546
Algorithms for the study of episodic hormone secretion
Merriam, G. R., & Wachter, K. W. (1982) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1982.243.4.e310 · Cited by 1,221
A role for kisspeptins in the regulation of gonadotropin secretion in the mouse
Gottsch, M. L., Cunningham, M. J., Smith, J. T., Popa, S. M., Acohido, B. V., Crowley, W. F., Seminara, S., Clifton, D. K., & Steiner, R. A. (2004) · Endocrinology · doi:10.1210/en.2004-0431 · Cited by 1,161
KiSS-1, a Novel Human Malignant Melanoma Metastasis-Suppressor Gene
Lee, J.-H., Miele, M. E., Hicks, D. J., Phillips, K. K., Trent, J. M., Weissman, B. E., & Welch, D. R. (1996) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/88.23.1731 · Cited by 1,072
Han, S.-K., Gottsch, M. L., Lee, K. J., Popa, S. M., Smith, J. T., Jakawich, S. K., Clifton, D. K., Steiner, R. A., & Herbison, A. E. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.3328-05.2005 · Cited by 1,036
Irwig, M. S., Fraley, G. S., Smith, J. T., Acohido, B. V., Popa, S. M., Cunningham, M. J., Gottsch, M. L., Clifton, D. K., & Steiner, R. A. (2004) · Neuroendocrinology · doi:10.1159/000083140 · Cited by 930
Gonadotropin-Releasing Hormone Receptors
Millar, R. P., Lu, Z.-L., Pawson, A. J., Flanagan, C. A., Morgan, K., & Maudsley, S. R. (2004) · Endocrine Reviews · doi:10.1210/er.2003-0002 · Cited by 791
Differential Regulation of KiSS-1 mRNA Expression by Sex Steroids in the Brain of the Male Mouse
Smith, J. T., Lemko, H. M. D., Stoll, E. A., Gottsch, M. L., Braun, R. E., Eacker, S. M., Clifton, D. K., & Steiner, R. A. (2005) · Endocrinology · doi:10.1210/en.2005-0323 · Cited by 717
Research works printed but not linked: 1
- 10.1210/en.143.6.2284 · DOI
Cited by
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Evaluating the potential utility of kisspeptin to treat reproductive disorders
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Christian, C. A. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-803592-4.00061-4 · Cited by 2
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Shashank, C. G., Kumar, N. A., & Banakar, P. S. (2018) · International Journal of Current Microbiology and Applied Sciences · doi:10.20546/ijcmas.2018.707.251 · Cited by 2
Kanasaki, H., Oride, A., Tumurbaatar, T., & Kyo, S. (2018) · IntechOpen eBooks · doi:10.5772/intechopen.73128 · Cited by 2
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Goodman, R. L., Coolen, L. M., & Lehman, M. N. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-819801-8.00019-3 · Cited by 2
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Vaudry, H. (2010) · Endocrinology · doi:10.1210/en.2009-1298 · Cited by 2
Milesi, S., Klosen, P., & Simonneaux, V. (2018) · doi:10.1002/9781119233275.ch16 · Cited by 2
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Mahmoudi, F., & Haghighat, K. (2020) · Galen Medical Journal · doi:10.31661/gmj.v9i.1767 · Cited by 1
Neve, V., Fernandois, D., Rai, S., Özorhan, Ü., Nampoothiri, S. S., Ternier, G., Sideromenos, S., Gallet, S., Allet, C., Stahr, M., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-74598-5 · Cited by 1
Ramzan, F., Qureshi, I., Khan, M. A., & Iqbal, M. J. (2013) · Pakistan Journal of Zoology · Cited by 1
Neuroendocrine Control of Human Testicular Function
Moore, J. P., & Winters, S. J. (2017) · Contemporary Endocrinology · doi:10.1007/978-3-319-53298-1_1 · Cited by 1
The interaction of prolactin and kisspeptin in conditions of normo- and hyperprolactinemia
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Phytoestrogens Responsible for Altered Pubertal Timing in Females: A Matter of Concern
Bhattacharya, S., & Paul, S. M. N. (2021) · Proceedings of the Zoological Society · doi:10.1007/s12595-021-00398-y · Cited by 1
Carrasco, R. A., Pezo, S., Zwiefelhofer, E. M., Lanigan, E., Singh, J. K., Berland, M., Ulloa-Leal, C., Ratto, M. H., & Adams, G. P. (2023) · Reproduction · doi:10.1530/rep-22-0331 · Cited by 1
The Role of Kisspeptin and KNDy Cells in the Reproductive Neuroendocrine System
Merkley, C. M. (2013) · Scholarship@Western (Western University) · Cited by 1
Rahdar, P., & Khazali, H. (2018) · International journal of basic science in medicine · doi:10.15171/ijbsm.2018.23 · Cited by 1
Kisspeptin Increases Luteinizing Hormone Secretion in Food Deprived D-Lys3-GHRP6-Treated Rats
Mahmoudi, F. (2017) · Galen Medical Journal · doi:10.31661/gmj.v6i1.811 · Cited by 1
Interactions of GPR54 and GPR147 receptors with RF-amide ligands
Hendrikse, M. (2014) · Open University of Cape Town (University of Cape Town) · Cited by 1
Loss of the habenula neuromodulator Kisspeptin1 disrupts learning in larval zebrafishPreprint
Lupton, C., Sengupta, M., Cheng, R.-K., Chia, J., Thirumalai, V., & Jesuthasan, S. (2016) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/080994 · Cited by 1
Modulators of GnRH Secretion and Therapeutic Applications
Newton, C. L., Anderson, R. C., & Millar, R. P. (2018) · Wiley eBooks · doi:10.1002/9781119233275.ch18 · Cited by 1
The Role of Kisspeptin in the Ovarian Cycle, Pregnancy, and Fertility
Ahart, E., Phillips, E., Wolfe, M. W., & Marsh, C. A. (2021) · IntechOpen eBooks · doi:10.5772/intechopen.98446 · Cited by 1
Bedenbaugh, M. N. (2018) · doi:10.33915/etd.5174 · Cited by 1
5 Infertility and assisted reproduction
Maclean, A. (2004) · Routledge eBooks · doi:10.4324/9781843148913-19 · Cited by 1
Cvetković, D. (2012) · Scholarship@Western (Western University)
GABA y receptores GABA B en el eje reproductivo: su relación con GnRH y kisspeptinas
Gessa, G. D., & Giorgio, N. P. D. (2013)
Walen, M. (2014) · Utrecht University Repository (Utrecht University)
Atia, R. R. A., & Abulfadle, K. A. (2014) · Basic Sciences of Medicine
Does Kisspeptin signaling offer a new way to treat infertility?
Jayasena, C. N., Dhillo, W. S., & Bloom, S. R. (2009) · Expert Review of Obstetrics & Gynecology · doi:10.1586/eog.09.28
Mechanism of gonadotropin releasing hormone (GnRH) pulse generation: A review
Nabi, G., Amin, M. A., Gul, N., Ali, S. M., & Khan, A. A. (2014)
Chambers, C. (2013) · Holmes Museum Of Anthropology (Wichita State University)
Plasma Kisspeptin Levels in Hypothyroidism and Premature Newborns
Kaya, A., Orbak, Z., Polat, H., Şebin, E., Polat, I., & Gülfidan, E. (2016) · West Indian Medical Journal · doi:10.7727/wimj.2015.287
Kisspeptina: efeito na maturação in vitro de ovócitos bovinos
Oliveira, M. (2016) · doi:10.14393/ufu.di.2016.24
Li, S. (2016) · Research Portal (King's College London)
Ruka, K. A. (2015) · Deep Blue (University of Michigan)
Friedman, Z. (2013) · TSpace (University of Toronto)
Effects of abnormal levels of testosterone on hypothalamic expression of kisspeptin in male rats
Salehi, M. S., Khazali, H., Mahmoudi, F., & Janahmadi, M. (2017) · Pars of Jahrom University of Medical Sciences · doi:10.29252/jmj.15.1.43
Methods of Sterilization and Contraception in Mammals
Ferro, V. A., Sliwowska, J. H., Qaraghuli, M. M. A., & Alsaadi, M. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-809633-8.20634-1
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Young, J., George, J. T., Tello, J. A., Francou, B., Bouligand, J., Guiochon‐Mantel, A., Brailly‐Tabard, S., Anderson, R. A., & Millar, R. P. (2016)
Rahdar, P., & Khazali, H. (2019) · International journal of basic science in medicine · doi:10.15171/ijbsm.2019.02
Davoodian, N., Khetvan-Hafshejani, R., Kadivar, A., Mousavi, M. M., Aali, E., Gheami, A., Moghaddam, B. B., & Shirian, S. (2019) · The Neuroscience Journal of Shefaye Khatam · doi:10.29252/shefa.7.3.74
Kisspeptin receptor (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Davenport, A. P., Maguire, J. J., & Mead, E. J. (2019) · IUPHAR/BPS Guide to Pharmacology CITE · doi:10.2218/gtopdb/f34/2019.4
Combinatorial Contributions of Kisspeptin Neurons and GnRH Neurons to Male Infertility
Han, H. I. (2014) · W&M Publish (College of William & Mary)
Identification of hypothalamic sites that control puberty onset and sexual maturation
Greenwald-Yarnell, M. L. (2013) · Deep Blue (University of Michigan)
Bellastella, A. (2012) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.14267154.15779314
Samson, W. K., & Yosten, G. L. C. (2011) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.13223962.14573061
Kisspeptin receptor (version 2020.4) in the IUPHAR/BPS Guide to Pharmacology Database
Davenport, A. P., Maguire, J. J., Mead, E. J., & Pawson, A. J. (2020) · IUPHAR/BPS Guide to Pharmacology CITE · doi:10.2218/gtopdb/f34/2020.4
Les peptides RFamide et leurs récepteurs dans la modulation de la douleur
Muller, C., Boyer, O., Gavériaux‐Ruff, C., & Simonin, F. (2022) · Douleur et Analgésie · doi:10.3166/dea-2022-0230
Kisspeptin receptor in GtoPdb v.2023.1
Davenport, A. P., Maguire, J. J., Mead, E. J., & Pawson, A. J. (2023) · IUPHAR/BPS Guide to Pharmacology CITE · doi:10.2218/gtopdb/f34/2023.1
Investigation of subfertility in the female Nsmf knockout mouse
Louden, E. D., Dougherty, M. P., Chorich, L. P., Eroğlu, A., & Layman, L. C. (2023) · F&S Science · doi:10.1016/j.xfss.2023.07.003
Kisspeptin Hormone: Revolution in Reproductive System Physiology
Abdelaziz, M. A. (2023) · International Journal of Biomedicine · doi:10.21103/article13(4)_ra1
Obezite ve Hipogonadizm İlişkisi
Çoşkun, G. (2025) · Arşiv Kaynak Tarama Dergisi · doi:10.17827/aktd.1651603
Endocrine-metabolic effects of kisspeptin in mammals
Pastor, F. M., Santos, B. R., Silva, J. F., Ocarino, N. M., & Serákides, R. (2026) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2026.114888
Bonomi, M., Vezzoli, V., Goggi, G., & Cariboni, A. M. (2026) · Endocrinology · doi:10.1007/978-3-319-29456-8_1-2
Research Progress on the Kisspeptin-GnRH Pathway in the Treatment of Polycystic Ovary Syndrome
陈, 建. (2026) · Advances in Clinical Medicine · doi:10.12677/acm.2026.1641314
Perturbation de la rythmicité circadienne : impact sur la fonction reproductive de souris femelles
Bahougne, T. (2020) · theses.fr (ABES) · doi:10.70675/f27b711fz7b99z44f6za0c5zaea6ee95b797
Pascali, F. D. (2019) · theses.fr (ABES) · doi:10.70675/0d58d2a7z9bffz44e4zb5f6z9cd3ef69d5c2
Kisspeptin-10 regulates glycosaminoglycan and decorin content in human cardiac fibroblast cultures
Radwańska, P., Olkiewicz, M., Piera, L., & Drobnik, J. (2026) · Pharmacological Reports · doi:10.1007/s43440-026-00870-6
The Mutual Modulation of Endocannabinoid and Kisspeptin Systems in Rat Testis
Mele, E., Ruggiero, M., Mazzeo, F., Viggiano, A., & Meccariello, R. (2026) · Endocrines · doi:10.3390/endocrines7030036
BindingDB Entry 50039388: Activation of Neuropeptide FF Receptors by Kisspeptin Receptor Ligands.
BindingDB (2013) · UC San Diego · doi:10.7270/q2k07586
Pathway-Specific Signaling and its Impact on Fertility: A Focus on the Kisspeptin Receptor, Kiss1r
Ahow, M. R. (2014) · Scholarship@Western (Western University)
Metadata
- Authors
- Roseweir, A. K., Kauffman, A. S., Smith, J. T., Guerriero, K. A., Morgan, K., Pielecka-Fortuna, J., Pineda, R., Gottsch, M. L., Tena-Sempere, M., Moenter, S. M., Terasawa, E., Clarke, I. J., Steiner, R. A., & Millar, R. P.
- Affiliations
- The Queen's Medical Research Institute (GB)
- University of Washington (US)
- Monash University (AU)
- University of Wisconsin–Madison (US)
- University of Virginia (US)
- Universidad de Córdoba (CO)
- University of Cape Town (ZA)
- Corresponding author
- Millar, Robert P.
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2009-03-25
- Volume
- 29
- Issue
- 12
- Pages
- 3920-3929
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3035813
- OpenAlex
- W2058657335
- Cited by
- 379
- References
- 53
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 7 · 2023: 9 · 2022: 14 · 2021: 18 · 2020: 17 · 2019: 14 · 2018: 26 · 2017: 25 · 2016: 20 · 2015: 34 · 2014: 39 · 2013: 39 · 2012: 29
- FWCI
- 39.79
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Funders
- National Institutes of Health (5u54hd012629-31)
- U.S. Public Health Service (K99 056157)
- Medical Research Council (MC_EX_G0701682)
- National Health and Medical Research Council
- Instituto de Salud Carlos III (PI042082, RCMN C03/08, C03/08)
- National Institute of Child Health and Human Development
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD 27142, R01-HD-11355, R01HD41469, R01HD015433, R01 HD15433, U54-HD-12629, U54HD-012629, K99HD056157, R01HD011355, R01HD027142, R01HD041469)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- kisspeptin, kisspeptin-10, GnRH neurons, gonadotropin regulation, puberty onset, luteinizing hormone secretion, neuroendocrine regulation of reproduction, precocious puberty, endometriosis, metastatic prostate cancer
- MeSH terms
- Receptors, Kisspeptin-1, Action Potentials, Animals, Brain, Castration, Cricetulus, Female, Cricetinae, Humans, Luteinizing Hormone, Gonadotropin-Releasing Hormone, Macaca mulatta, Male, Peptides, Sheep, Structure-Activity Relationship, CHO Cells, Microdialysis, Tumor Suppressor Proteins, Receptors, G-Protein-Coupled, Mice, Rats, Kisspeptins, In Vitro Techniques
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