The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54
Open accessAbstract
Hypogonadotropic hypogonadism is defined as a deficiency of the pituitary secretion of follicle-stimulating hormone and luteinizing hormone, which results in the impairment of pubertal maturation and of reproductive function. In the absence of pituitary or hypothalamic anatomical lesions and of anosmia (Kallmann syndrome), hypogonadotropic hypogonadism is referred to as isolated hypogonadotropic hypogonadism (IHH). A limited number of IHH cases are due to loss-of-function mutations of the gonadotropin-releasing hormone receptor. To identify additional gene defects leading to IHH, a large consanguineous family with five affected siblings and with a normal gonadotropin-releasing hormone receptor coding sequence was studied. Homozygosity whole-genome mapping allowed the localization of a new locus within the short arm of chromosome 19 (19p13). Sequencing of several genes localized within this region showed that all affected siblings of the family carried a homozygous deletion of 155 nucleotides in the GPR54 gene. This deletion encompassed the splicing acceptor site of intron 4-exon 5 junction and part of exon 5. The deletion was absent or present on only one allele in unaffected family members. GPR54 has been initially identified as an orphan G protein-coupled receptor with 40% homology to galanin receptors. Recently, a 54-aa peptide derived from the KiSS1 protein was identified as a ligand of GPR54. The present study shows that loss of function of GPR54 is a cause of IHH, and it identifies GPR54 and possibly KiSS1 protein-derived peptide as playing a major and previously unsuspected role in the physiology of the gonadotropic axis.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“loss-of-function mutations in the kisspeptin receptor cause GnRH deficiency in humans and mice (16-18).”
From Kisspeptin Overcomes GnRH Neuronal Suppression Secondary to Hyperprolactinemia in Humans (2022) · cites this paper as [16]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“both humans and rodents with inactivating mutations in kisspeptin or its receptor fail to progress through puberty or show normal pulsatile LH secretion (Seminara et al., 2003;de Roux et al., 2003;Kaiser, 2015).”
From The Origin of GnRH Pulse Generation: An Integrative Mathematical-Experimental Approach (2019) · cites this paper as de Roux et al., 2003
Experimental — accuracy not yet measuredIn the citing paper
“The discovery of the kisspeptin system as a crucial component for pubertal activation of the hypothalamic-pituitary-gonadal axis occurred in 2003, when loss-of-function mutations of the KISS1R (previously known as GPR54) gene were identified in individuals with isolated hypogonadotropic hypogonadism, establishing KISS1R inactivation as a cause of this disorder (table, figure 2).42,43”
From Pubertal development and regulation (2016) · cites this paper as [42]
In the citing paper
“Two of the most important excitatory components of the GnRH network were identified with the demonstration that the genetic loss of such inputs results in failure to initiate the GnRH pulse generator at the expected time of puberty, resulting in isolated hypogonadotropic hypogonadism.42–45”
From Pubertal development and regulation (2016) · cites this paper as [42]
In the citing paper
“Although studies in animals have led to identification of regulators of GnRH such as catecholamines, GABA, and glutamate, genetic studies of patients with pubertal disorders have resulted in the identification of a major regulatory hub for the GnRH neurons—ie, the hypothalamic neurons expressing kisspeptin and neurokinin B.42–44”
From Pubertal development and regulation (2016) · cites this paper as [42]
In the citing paper
“The reproductive roles of the G-protein-coupled KiSS-1 receptor (also known as GPR54, encoded by KISS1R) and its endogenous ligand, kisspeptin 1 (encoded by KISS1) were revealed in 2003 when inactivating mutations in the KiSS-1 receptor were found in the homozygous state in members of two large, consanguineous families with a history of normosmic IHH.”
From The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism (2009) · cites this paper as [34]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
A comprehensive genetic map of the human genome based on 5,264 microsatellites
Dib, C., Fauré, S., Fizames, C., Samson, D. S., Drouot, N., Alain Vignal, A., Millasseau, P., Marc, S., Kazan, J., Seboun, E., et al. (1996) · Nature · doi:10.1038/380152a0 · Cited by 2,927
Parametric and nonparametric linkage analysis: a unified multipoint approach.
Kruglyak, L., Daly, M. J., Daly, M. J., & Lander, E. S. (1996) · PubMed Central · Cited by 2,883
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
Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor
Ohtaki, T., Shintani, Y., Honda, S., Matsumoto, H., Hori, A., Kanehashi, K., Terao, Y., Kumano, S., Takatsu, Y., Masuda, Y., et al. (2001) · Nature · doi:10.1038/35079135 · Cited by 1,447
Faster sequential genetic linkage computations.
Cottingham, R. W., Idury, R. M., & Schäffer, A. A. (1993) · Europe PMC (PubMed Central) · Cited by 1,364
Uncovering Molecular Mechanisms Involved in Activation of G Protein-Coupled Receptors
Gether, U. (2000) · Endocrine Reviews · doi:10.1210/edrv.21.1.0390 · Cited by 1,264
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
AXOR12, a Novel Human G Protein-coupled Receptor, Activated by the Peptide KiSS-1
Muir, A. I., Chamberlain, L., Elshourbagy, N. A., Michalovich, D., Moore, D. J., Calamari, A., Szekeres, P. G., Sarau, H. M., Chambers, J. K., Murdock, P. R., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m102743200 · Cited by 906
Franco, B., Guioli, S., Pragliola, A., Incerti, B., Bardoni, B., Tonlorenzi, R., Carrozzo, R., Maestrini, E., Pieretti, M., Taillon-Miller, P., et al. (1991) · Nature · doi:10.1038/353529a0 · Cited by 846
Loss-of-function mutations in FGFR1 cause autosomal dominant Kallmann syndrome
Dodé, C., Levilliers, J., Dupont, J., Paepe, A. D., Dû, N. L., Soussi‐Yanicostas, N., Coimbra, R. S., Delmaghani, S., Nouaille, S., Baverel, F., et al. (2003) · Nature Genetics · doi:10.1038/ng1122 · Cited by 839
Flagged first, then by citations
Research works printed but not linked: 3
- Beranova, M., Oliveira, L. M., Bedecarrats, G. Y., Schipani, E., Vallejo, M., Ammini, A. C., Quintos, J. B., Hall, J. E., Martin, K. A., Hayes, F. J., et al. (2001) J. Clin. Endocrinol. Metab. 86, 1580–1588.11297587
- Cottingham, R. W., Jr., Idury, R. M. & Schaffer, A. A. (1993) Am. J. Hum. Genet. 53, 252–263.8317490
- Kruglyak, L., Daly, M. J., Reeve-Daly, M. P. & Lander, E. S. (1996) Am. J. Hum. Genet. 58, 1347–1363.8651312
Cited by
Sorted by citations
Items 301–400 of 1,003
Sex steroid control of hypothalamic Kiss1 expression in sheep and rodents: Comparative aspects
Smith, J. T. (2008) · Peptides · doi:10.1016/j.peptides.2008.08.013 · Cited by 119
“Genetic studies from two independent laboratories discovered that disabling mutations and targeted deletions of the G protein-coupled receptor, GPR54, in humans and mice result in sexual infantilism and hypogonadotropic hypogonadism [15,54].”
BackgroundFeinberg, I., Higgins, L. M., Khaw, W. Y., & Campbell, I. G. (2006) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00293.2006 · Cited by 118
Kisspeptin/Gpr54‐Independent Gonadotrophin‐Releasing Hormone Activity in Kiss1 and Gpr54 Mutant Mice
Chan, Y.-M., Broder‐Fingert, S., Wong, K. M., & Seminara, S. B. (2009) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2009.01926.x · Cited by 114
Brioude, F., Bouligand, J., Trabado, S., Francou, B., Salenave, S., Kamenický, P., Brailly‐Tabard, S., Chanson, P., Guiochon‐Mantel, A., & Young, J. (2010) · European Journal of Endocrinology · doi:10.1530/eje-10-0083 · Cited by 114
Mead, E. J., Maguire, J. J., Kuc, R. E., & Davenport, A. P. (2007) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707295 · Cited by 116
“KISS1 (GPR54) – an unexpected molecular switch for puberty In 2003, three different groups identified KISS1 (GPR54) as an unexpected molecular switch for puberty (de Roux et al., 2003; Funes et al., 2003; Seminara et al., 2003).”
BackgroundKisspeptin resets the hypothalamic GnRH clock in men
Chan, Y.-M., Butler, J. P., Pinnell, N. E., Pralong, F. P., Crowley, W. F., Ren, C., Chan, K. K., & Seminara, S. B. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-3046 · Cited by 114
Caron, É., Ciofi, P., Prévot, V., & Bouret, S. G. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.6074-11.2012 · Cited by 112
“…structural alterations in kisspeptin circuits Because kisspeptin neurons have been reported to play a central role in pubertal activation (de Roux et al., 2003; Seminara et al., 2003), and because kisspeptin neural circuits develop gradually during the first 2–5 weeks of postnatal life…”
BackgroundMutations in the maternally imprinted gene MKRN3 are common in familial central precocious puberty
Simon, D., Ba, I., Mekhail, N., Écosse, E., Paulsen, A., Zénaty, D., Houang, M., Jésuran-Pérelroizen, M., FILIPPO, G. D., Salerno, M., et al. (2015) · European Journal of Endocrinology · doi:10.1530/eje-15-0488 · Cited by 115
“82 Estradiol (pg/mL) 19 (9-28) 16 (7-31) 0.”
MethodMini-Puberty, Physiological and Disordered: Consequences, and Potential for Therapeutic Replacement
Rohayem, J., Alexander, E. C., Heger, S., Nordenström, A., & Howard, S. R. (2024) · Endocrine Reviews · doi:10.1210/endrev/bnae003 · Cited by 127
Poling, M. C., Quennell, J. H., Anderson, G. M., & Kauffman, A. S. (2013) · Journal of Neuroendocrinology · doi:10.1111/jne.12084 · Cited by 112
Qiu, X., Dowling, A. R., Marino, J. S., Faulkner, L. D., Bryant, B., Brüning, J. C., Elias, C. F., & Hill, J. W. (2013) · Endocrinology · doi:10.1210/en.2012-2056 · Cited by 114
Reproductive functions of Kisspeptin/KISS1R Systems in the Periphery
Cao, Y., Li, Z., Jiang, W., Yan, L., & Kuang, H. (2019) · Reproductive Biology and Endocrinology · doi:10.1186/s12958-019-0511-x · Cited by 116
Pubertal Development and Menarche
DiVall, S. A., & Radovick, S. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1429.026 · Cited by 110
Kirby, H. R., Maguire, J. J., Colledge, W. H., & Davenport, A. P. (2010) · Pharmacological Reviews · doi:10.1124/pr.110.002774 · Cited by 115
“Initial reports of kisspeptin expression reported high levels in the human placenta (Lee et al., 1996; Muir et al., 2001; Ohtaki et al., 2001).”
BackgroundInfluentialZhang, C., Bosch, M. A., Rønnekleiv, O. K., & Kelly, M. J. (2009) · Endocrinology · doi:10.1210/en.2008-1313 · Cited by 114
Constantin, S., Caligioni, C. S., Stojilković, S. S., & Wray, S. (2008) · Endocrinology · doi:10.1210/en.2008-0979 · Cited by 114
Hypothesis: Kisspeptin Mediates Male Hypogonadism in Obesity and Type 2 Diabetes
George, J. T., Millar, R. P., & Anderson, R. A. (2010) · Neuroendocrinology · doi:10.1159/000299767 · Cited by 110
Bhagavath, B., Podolsky, R. H., Özata, M., Bolu, E., Bick, D. P., Kulharya, A. S., Sherins, R. J., & Layman, L. C. (2006) · Fertility and Sterility · doi:10.1016/j.fertnstert.2005.08.044 · Cited by 110
Coming of age in the Kisspeptin Era: Sex differences, development, and puberty
Kauffman, A. S. (2010) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2010.01.017 · Cited by 106
“In 2003, Seminara and colleagues and de Roux et al. independently reported that puberty was dramatically impaired in humans with spontaneous mutations in the Kiss1R gene (de Roux et al. 2003; Seminara et al. 2003).”
BackgroundMitani, Y., Kanda, S., Akazome, Y., Zempo, B., & Oka, Y. (2010) · Endocrinology · doi:10.1210/en.2009-1174 · Cited by 111
“show hypogonadotropic hypogonadism (5, 6).”
Update on the Genetics of Idiopathic Hypogonadotropic Hypogonadism
Topaloglu, A. K. (2018) · Journal of Clinical Research in Pediatric Endocrinology · doi:10.4274/jcrpe.2017.s010 · Cited by 112
“Mutations in KISS1R were first reported in IHH familial multiplex cases in 2003 (73,74).”
BackgroundCellular and molecular features of EDC exposure: consequences for the GnRH network
Rodríguez, D. L., Franssen, D., Bakker, J., Lomniczi, A., & Parent, A. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-020-00436-3 · Cited by 112
Neuroendocrine Impairments of Polycystic Ovary Syndrome
Ruddenklau, A., & Campbell, R. E. (2019) · Endocrinology · doi:10.1210/en.2019-00428 · Cited by 116
de Croft, S., Piet, R., Mayer, C., Mai, O., Boehm, U., & Herbison, A. E. (2012) · Endocrinology · doi:10.1210/en.2012-1616 · Cited by 101
“tile (1,2), a considerable efforthas focusedonunderstanding”
Adipose tissue and reproductive health
Mathew, H., Castracane, V. D., & Mantzoros, C. S. (2017) · Metabolism · doi:10.1016/j.metabol.2017.11.006 · Cited by 109
Uenoyama, Y., Nagae, M., Tsuchida, H., Inoue, N., & Tsukamura, H. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.724632 · Cited by 118
Morelli, A., Sarchielli, E., Comeglio, P., Filippi, S., Vignozzi, L., Marini, M., Rastrelli, G., Maneschi, E., Cellai, I., Persani, L., et al. (2014) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2013.09.017 · Cited by 107
“As is well established, the kisspeptin/KISS1 receptor (KISS1R/GPR54) system plays a major role in the central control of GnRH axis (de Roux et al., 2003; Seminara et al., 2003).”
BackgroundCurrent and future applications of GnRH, kisspeptin and neurokinin B analogues
Millar, R. P., & Newton, C. L. (2013) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2013.120 · Cited by 107
Uenoyama, Y., Inoue, N., Pheng, V., Homma, T., Takase, K., Yamada, S., Ajiki, K., Ichikawa, M., Okamura, H., Maeda, K., et al. (2011) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2011.02199.x · Cited by 106
Plant, T. M. (2008) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2008.01708.x · Cited by 105
Leka-Emiri, S., Chrousos, G. P., & Kanaka‐Gantenbein, C. (2017) · Journal of Endocrinological Investigation · doi:10.1007/s40618-017-0627-9 · Cited by 103
Hypopituitarism: Clinical Features, Diagnosis, and Management
Toogood, A. A., & Stewart, P. M. (2008) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2007.10.004 · Cited by 105
Centrally injected kisspeptin reduces food intake by increasing meal intervals in mice
Stengel, A., Wang, L., Goebel‐Stengel, M., & Taché, Y. (2011) · Neuroreport · doi:10.1097/wnr.0b013e32834558df · Cited by 108
Guerriero, K. A., Keen, K. L., Millar, R. P., & Terasawa, E. (2011) · Endocrinology · doi:10.1210/en.2011-1565 · Cited by 106
“senceofpuberty inhumans(5,6),andevidencefromtransgenic”
Kisspeptin and the seasonal control of reproduction in hamsters
Simonneaux, V., Ansel-Bollepalli, L., Revel, F. G., Klosen, P., Pévet, P., & Mikkelsen, J. D. (2008) · Peptides · doi:10.1016/j.peptides.2008.06.006 · Cited by 114
“[8] de Roux N, Genin E, Carel JC, Matsuda F, Chaussain JL, Milgrom E.”
BackgroundMetastin/Kisspeptin and control of estrous cycle in rats
Maeda, K., Adachi, S., Inoue, K., Ohkura, S., & Tsukamura, H. (2007) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-007-9032-6 · Cited by 108
“Two independent studies [13, 14] showed that individuals lacking GPR54 never experience puberty.”
BackgroundDriving reproduction: RFamide peptides behind the wheel
Kriegsfeld, L. J. (2006) · Hormones and Behavior · doi:10.1016/j.yhbeh.2006.06.004 · Cited by 108
“by Dockray et al. (1983) (and see above) is a fragment of the GnIH precursor (Dockray et al.”
Francou, B., Bouligand, J., Voican, A., Amazit, L., Trabado, S., Fagart, J., Méduri, G., Brailly‐Tabard, S., Chanson, P., Lecomte, P., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025614 · Cited by 109
The Congenital and Acquired Mechanisms Implicated in the Etiology of Central Precocious Puberty
Brito, V. N., Canton, A. P. M., Seraphim, C. E., Abreu, A. P., Macedo, D. B., Mendonca, B. B., Kaiser, U. B., Argente, J., & Latronico, A. C. (2022) · Endocrine Reviews · doi:10.1210/endrev/bnac020 · Cited by 119
Roa, J., Vigo, E., García-Galiano, D., Castellano, J. M., Navarro, V. M., Pineda, R., Diéguez, C., Aguilar, E., Pinilla, L., & Tena‐Sempere, M. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90240.2008 · Cited by 104
Potential roles for the kisspeptin/kisspeptin receptor system in implantation and placentation
Hu, K.-L., Chang, H., Zhao, H., Yu, Y., Li, R., & Qiao, J. (2018) · Human Reproduction Update · doi:10.1093/humupd/dmy046 · Cited by 110
“In humans, kisspeptin was initially implicated in the onset of puberty as two independent research groups reported KISS1R gene mutations in patients with idiopathic hypogonadotropic hypogonadism (IHH) (de Roux et al., 2003; Seminara et al., 2003).”
BackgroundEstrogenic Regulation of the GnRH Neuron
Radovick, S., Levine, J. E., & Wolfe, A. (2012) · Frontiers in Endocrinology · doi:10.3389/fendo.2012.00052 · Cited by 102
“The recent description of a patient with idiopathic hypogonadotropic hypogonadism with a mutation in a G-protein coupled receptor, referred to as GPR54, has added to our knowledge of signaling pathways involved in this complex system (de Roux et al., 2003; Seminara et al., 2003).”
BackgroundBAX-Dependent and BAX-Independent Regulation of Kiss1 Neuron Development in Mice
Semaan, S. J., Murray, E. K., Poling, M. C., Dhamija, S., Forger, N. G., & Kauffman, A. S. (2010) · Endocrinology · doi:10.1210/en.2010-0783 · Cited by 107
“The Kiss1 gene, and its protein product kisspeptin, has recently been shown to be critical for puberty onset and adult fertility (20, 21).”
Chaudhary, H., Patel, J. K., Jain, N. K., & Joshi, R. G. (2021) · Journal of Ovarian Research · doi:10.1186/s13048-021-00879-w · Cited by 108
Kisspeptin and Puberty in Mammals
Terasawa, E., Guerriero, K. A., & Plant, T. M. (2013) · Advances in experimental medicine and biology · doi:10.1007/978-1-4614-6199-9_12 · Cited by 107
“(2) first described amino acid mutations of KISS1R in human patients with a delay in puberty onset or an abnormality in pubertal development.”
BackgroundClarkson, J., & Herbison, A. E. (2011) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2011.02107.x · Cited by 104
Panidis, D., Rousso, D., Koliakos, G., Kourtis, A., Katsikis, I., Farmakiotis, D., Votsi, E., & Diamanti‐Kandarakis, E. (2006) · Fertility and Sterility · doi:10.1016/j.fertnstert.2005.11.044 · Cited by 103
Chan, Y.-M., Butler, J. P., Sidhoum, V. F., Pinnell, N. E., & Seminara, S. B. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-1282 · Cited by 100
Insulin: Its role in the central control of reproduction
Sliwowska, J. H., Fergani, C., Gawałek, M., Skowrońska, B., Fichna, P., & Lehman, M. N. (2014) · Physiology & Behavior · doi:10.1016/j.physbeh.2014.05.021 · Cited by 104
“12 of the kisspeptin receptor KISS1R (GPR54), lead hypogonadotropic hypogonadism in humans, and a 390 failure to enter puberty [128, 129].”
Nakajo, M., Kanda, S., Karigo, T., Takahashi, A., Akazome, Y., Uenoyama, Y., Kobayashi, M., & Oka, Y. (2017) · Endocrinology · doi:10.1210/en.2017-00808 · Cited by 104
Maione, L., Bouvattier, C. M., & Kaiser, U. B. (2021) · Clinical Endocrinology · doi:10.1111/cen.14475 · Cited by 113
Characterization of the kisspeptin system in human spermatozoa
Pinto, F. M., Cejudo-Román, A., Ravina, C. G., Sánchez, M. F., Martín-Lozano, D., Illanes, M., Tena‐Sempere, M., & Candenas, L. (2011) · International Journal of Andrology · doi:10.1111/j.1365-2605.2011.01177.x · Cited by 102
Human GnRH Deficiency: A Unique Disease Model to Unravel the Ontogeny of GnRH Neurons
Balasubramanian, R., Dwyer, A. A., Seminara, S. B., Pitteloud, N., Kaiser, U. B., & Crowley, W. F. (2010) · Neuroendocrinology · doi:10.1159/000314193 · Cited by 104
Molecular Pathogenesis of Kallmann’s Syndrome
Cadman, S. M., Kim, S., Hu, Y., González-Martı́nez, D., & Bouloux, P.-M. G. (2006) · Hormone Research in Paediatrics · doi:10.1159/000098156 · Cited by 102
Selvaraj, S., Kitano, H., Fujinaga, Y., Ohga, H., Yoneda, M., Yamaguchi, A., Shimizu, A., & Matsuyama, M. (2010) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2010.07.011 · Cited by 101
Khan, A. R., & Kauffman, A. S. (2012) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2011.02162.x · Cited by 99
Shift in Kiss1 Cell Activity Requires Estrogen Receptor α
Frazão, R., Cravo, R. M., Donato, J., Ratra, D. V., Clegg, D. J., Elmquist, J. K., Zigman, J. M., Williams, K. W., & Elias, C. F. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.1610-12.2013 · Cited by 101
“Inactivating mutations of the KISS1/Kiss1 gene or of kisspeptin receptor (GPR54/Gpr54) gene cause lack of sexual maturation and infertility (Funes et al., 2003; Seminara et al., 2003; de Roux et al., 2003; Lapatto et al., 2007; d’Anglemont de Tassigny et al., 2007; Topaloglu et al., 2012).”
BackgroundKisspeptin and GnRH Pulse Generation
Okamura, H., Tsukamura, H., Ohkura, S., Uenoyama, Y., Wakabayashi, Y., & Maeda, K. (2013) · Advances in experimental medicine and biology · doi:10.1007/978-1-4614-6199-9_14 · Cited by 101
Ansel-Bollepalli, L., Bolborea, M., Bentsen, A. H., Klosen, P., Mikkelsen, J. D., & Simonneaux, V. (2010) · Journal of Biological Rhythms · doi:10.1177/0748730410361918 · Cited by 101
“…hypogonadic phenotype in mice (d’Anglemont de Tassigny et al., 2007; Funes et al., 2003; Lapatto et al., 2007; Seminara et al., 2003) and humans (de Roux et al., 2003), indicating that kisspeptins play a pivotal role in the maturation and the regulation of the hypothalamopituitary gonadotropic…”
BackgroundNeuroanatomical Evidence That Kisspeptin Directly Regulates Isotocin and Vasotocin Neurons
Kanda, S., Akazome, Y., Mitani, Y., Okubo, K., & Oka, Y. (2013) · PLoS ONE · doi:10.1371/journal.pone.0062776 · Cited by 101
Raivio, T., Sidis, Y., Plummer, L., Chen, H., Ma, J., Mukherjee, A., Jacobson-Dickman, E. E., Quinton, R., Vliet, G. V., Lavoie, H. B., et al. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-0179 · Cited by 100
“J Clin Invest 117:457–463 13. de Roux N, Genin E, Carel JC, Matsuda F, Chaussain JL, Milgrom E 2003 Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54.”
BackgroundInfluentialNimri, R., Lebenthal, Y., Lazar, L., Chevrier, L., Phillip, M., Bar, M., Hernández, E., de Roux, N., & Gat‐Yablonski, G. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-1676 · Cited by 102
“In the last decade, a number ofgeneticdefects at various siteshavebeen identifiedas causing normosmic IHH (1, 2), including in the GnRH receptor (GnRHR) (3), the G protein-coupled receptor-54 (GPR54) (4, 5),thenasalembryonicLHRHfactor(NELF)(6),thefibroblast growth factor receptor-1 (FGFR1) (7), the fibroblast growth f…”
BackgroundResultInfluentialSun, L., Wang, Y., Zhao, Y., Wang, H., Li, N., & Ji, X. S. (2016) · PLoS ONE · doi:10.1371/journal.pone.0158483 · Cited by 97
“The kisspeptin/gpr54 signaling system stimulates gonadotropin release [45,46].”
BackgroundA novel neuropeptide in suppressing luteinizing hormone release in goldfish, Carassius auratus
Liu, Y., Li, S., Xing, Q., Zhou, W., Liu, X., Lin, H., Zhang, Y., & Cheng, C. H. K. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2013.04.008 · Cited by 97
Roa, J., & Tena‐Sempere, M. (2007) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2007.01.026 · Cited by 98
Hiney, J. K., Srivastava, V. K., Pine, M. D., & Dees, W. L. (2008) · Endocrinology · doi:10.1210/en.2008-0954 · Cited by 99
Luque, R. M., Córdoba‐Chacón, J., Gahete, M. D., Navarro, V. M., Tena‐Sempere, M., Kineman, R. D., & Castano, J. P. (2011) · Endocrinology · doi:10.1210/en.2010-1142 · Cited by 99
“mutations of GPR54 in humans and rodents (1, 2).”
BackgroundKisspeptin neurons from mice to men: similarities and differences
Goodman, R. L., & Lehman, M. N. (2012) · Endocrinology · doi:10.1210/en.2012-1550 · Cited by 103
Melatonin Controls Seasonal Breeding by a Network of Hypothalamic Targets
Revel, F. G., Masson‐Pévet, M., Pévet, P., Mikkelsen, J. D., & Simonneaux, V. (2009) · Neuroendocrinology · doi:10.1159/000219588 · Cited by 99
“Unexpectedly, key genetic studies in 2003 demonstrated that humans and mice bearing loss-of-function mutations in the GPR54 gene displayed the symptoms of idiopathic hypogonadotropic hypogonadism, with abnormal sexual development and failure to undergo puberty [”
BackgroundShibata, M., Friedman, R. L., Ramaswamy, S., & Plant, T. M. (2007) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2007.01549.x · Cited by 102
The role of KiSS-1 in the regulation of puberty in higher primates
Plant, T. M. (2006) · European Journal of Endocrinology · doi:10.1530/eje.1.02232 · Cited by 97
Kisspeptins and RFRP-3 Act in Concert to Synchronize Rodent Reproduction with Seasons
Simonneaux, V., Ancel, C., Poirel, V., & Gauer, F. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2013.00022 · Cited by 100
“In 2003, the discovery that loss-of-function mutations of the gene encoding the Kp receptor Kiss1r/GPR54 in humans and rodents (de Roux et al., 2003; Seminara et al., 2003) prevent pubertal development and cause infertility spurred great interest in the role and mechanism of action of Kps in…”
BackgroundKisspeptin receptor agonist has therapeutic potential for female reproductive disorders
Abbara, A., Eng, P. C., Phylactou, M., Clarke, S. A., Richardson, R. E., Sykes, C. M., Phumsatitpong, C., Mills, E., Modi, M., Izzi‐Engbeaya, C. N., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci139681 · Cited by 100
Control of GnRH secretion: One step back
Clarke, I. J. (2011) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2011.01.001 · Cited by 96
“A significant advance was the discovery that the kisspeptin receptor (and by implication, its ligand, kisspeptin) was essential for normal reproduction [39,108].”
BackgroundMartin, C., Navarro, V. M., Simavlı, S. A., Vong, L., Carroll, R. S., Lowell, B. B., & Kaiser, U. B. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.3003-13.2014 · Cited by 90
“Kisspeptin secretion is essential for pubertal progression (de Roux et al., 2003; Seminara et al., 2003), and changes in kisspeptin tone induce changes in the timing of puberty onset in rodents and humans (Navarro et al., 2004; Silveira et al., 2013).”
BackgroundMKRN3 inhibits the reproductive axis through actions in kisspeptin-expressing neurons
Abreu, A. P., Toro, C. A., Song, Y. B., Navarro, V. M., Bosch, M. A., Eren, A., Liang, J. N., Carroll, R. S., Latronico, A. C., Rønnekleiv, O. K., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci136564 · Cited by 97
Peng, J., Tang, M., Zhang, B.-P., Zhang, P., Zhong, T., Zong, T., Yang, B., & Kuang, H. (2013) · Fertility and Sterility · doi:10.1016/j.fertnstert.2012.12.008 · Cited by 96
What controls the timing of puberty? An update on progress from genetic investigation
Gajdos, Z. K. Z., Hirschhorn, J. N., & Palmert, M. R. (2009) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0b013e328320253c · Cited by 95
Pielecka-Fortuna, J., & Moenter, S. M. (2009) · Endocrinology · doi:10.1210/en.2009-0692 · Cited by 95
Physiology of Gnrh and Gonadotropin Secretion
Marques, P., Skorupskaite, K., George, J. T., & Anderson, R. A. (2015) · Cited by 95
Ohga, H., Selvaraj, S., & Matsuyama, M. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00147 · Cited by 96
“Comp Biochem Physiol A Mol Integr Physiol (2012) 162(4):364–71.”
BackgroundMorrison, A., Fleming, S., & Levy, M. J. (2020) · Clinical Endocrinology · doi:10.1111/cen.14399 · Cited by 108
True, C. A., Kirigiti, M. A., Kievit, P., Grove, K. L., & Smith, M. S. (2011) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2011.02144.x · Cited by 93
Losa-Ward, S. M., Todd, K. L., Sullivan, A. W., Cao, J., Mickens, J. A., & Patisaul, H. B. (2010) · Reproductive Toxicology · doi:10.1016/j.reprotox.2010.10.002 · Cited by 93
“Humans (or mice) with a mutated form of Kiss1r fail to enter puberty and remain hypogonadal throughout life [5–6].”
BackgroundIwasa, T., Matsuzaki, T., Murakami, M., FUJISAWA, S., Kinouchi, R., Gereltsetseg, G., Kuwahara, A., Yasui, T., & Irahara, M. (2010) · The Journal of Physiology · doi:10.1113/jphysiol.2009.183558 · Cited by 95
“In humans, mutations in the gene for the kisspeptin receptor, Kiss1r, were identified in patients with idiopathic hypogonadotropic hypogonadism (de Roux et al. 2003; Seminara et al. 2003).”
BackgroundPlant, T. M. (2012) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2012.02.002 · Cited by 93
Gonadotropin-releasing hormone plasticity: A comparative perspective
Stevenson, T. J., Hahn, T. P., MacDougall‐Shackleton, S. A., & Ball, G. F. (2012) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2012.09.001 · Cited by 94
“In 2003, the endogenous receptor for the neuropeptide kisspeptin (KiSS1), GPR54, was identified, along with the observation that endogenous and genetically engineered mutation of the Gpr54 gene was associated with hypogonadotropic hypogonadism (De Roux et al., 2003; Seminara et al., 2003).”
BackgroundDevelopmental Changes in the Expression of Kisspeptin mRNA in Rat Hypothalamus
Takumi, K., Iijima, N., & Ozawa, H. (2010) · Journal of Molecular Neuroscience · doi:10.1007/s12031-010-9430-1 · Cited by 94
“Following the discovery of inactivating mutations in the GPR-54 gene associated with hypogonadotropic-hypogonadism in humans ( de Roux et al. 2003; Seminara et al. 2003), accumulating evidence has suggested the pivotal role of kisspeptin/GPR-54 system in mammalian reproductive functions.”
BackgroundInfluentialEndocrine Dysregulation in Anorexia Nervosa Update
Miller, K. K. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-1222 · Cited by 98
“Acute, but not chronic, administration of kisspeptin has been shown to result in gonadotropin release in women with hypothalamic amenorrhea (21), and inactivating mutations cause pubertal failure (22, 23).”
BackgroundEvans, J. J., & Anderson, G. M. (2012) · Human Reproduction Update · doi:10.1093/humupd/dms004 · Cited by 101
Chehab, F. F. (2014) · Journal of Endocrinology · doi:10.1530/joe-14-0413 · Cited by 93
“Kisspeptin emerged as a primary puberty candidate factor following the findings that subjects with hypogonadotropic hypogonadism carry mutations in the kisspeptin receptor GPR54 (KISS1R; de Roux et al. 2003, Seminara et al. 2003, Semple et al. 2005).”
Castellano, J. M., Navarro, V. M., Roa, J., Pineda, R., Sanchez-Garrido, M. A., García-Galiano, D., Vigo, E., Diéguez, C., Aguilar, E., Pinilla, L., et al. (2008) · Endocrinology · doi:10.1210/en.2008-0849 · Cited by 94
“aspects of reproductive maturation and function (11, 12).”
BackgroundDudek, M., Kolodziejski, P. A., Pruszyńska‐Oszmałek, E., Sassek, M., Ziarniak, K., Nowak, K. W., & Sliwowska, J. H. (2016) · Neuropeptides · doi:10.1016/j.npep.2016.01.005 · Cited by 96
Metastin and its G protein-coupled receptor, GPR54: Critical pathway modulating GnRH secretion
Seminara, S. B. (2005) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2005.10.001 · Cited by 91
Bakker, J., Pierman, S., & González-Martı́nez, D. (2009) · Hormones and Behavior · doi:10.1016/j.yhbeh.2009.11.005 · Cited by 91
“In recent years, the Kiss1 gene product, kisspeptin, has been proposed as an upstream regulator of the GnRH system as human patients did not enter into puberty due to a mutation in the GPR54 gene (de Roux et al., 2003), which encodes the kisspeptin receptor, named GPR54 (now named Kiss1r).”
RFamide Peptides: Structure, Function, Mechanisms and Pharmaceutical Potential
Findeisen, M., Rathmann, D., & Beck‐Sickinger, A. G. (2011) · Pharmaceuticals · doi:10.3390/ph4091248 · Cited by 89
Estrogen Regulates KiSS1 Gene Expression through Estrogen Receptor α and SP Protein Complexes
Li, D., Mitchell, D., Luo, J., Yi, Z., Cho, S.-G., Guo, J., Li, X., Ning, G., Wu, X., & Liu, M. (2007) · Endocrinology · doi:10.1210/en.2007-0154 · Cited by 90
Gill, J. C., Navarro, V. M., Kwong, C., Noel, S. D., Martin, C., Xu, S., Clifton, D. K., Carroll, R. S., Steiner, R. A., & Kaiser, U. B. (2012) · Endocrinology · doi:10.1210/en.2012-1529 · Cited by 90
Activation of Neuropeptide FF Receptors by Kisspeptin Receptor Ligands
Oishi, S., Misu, R., Tomita, K., Setsuda, S., Masuda, R., Ohno, H., Naniwa, Y., Ieda, N., Inoue, N., Ohkura, S., et al. (2010) · ACS Medicinal Chemistry Letters · doi:10.1021/ml1002053 · Cited by 90
Kisspeptin and GPR54: Discovery of a Novel Pathway in Reproduction
Seminara, S. B., & Crowley, W. F. (2008) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2008.01731.x · Cited by 90
Metadata
- Authors
- de Roux, N., Genin, E., Carel, J.-C., Matsuda, F., Chaussain, J.-L., & Milgrom, E.
- Affiliations
- Institut National de la Santé et de la Recherche Médicale Unité 135, Unité de Recherches Hormones Gènes et Reproduction, Hôpital de Bicêtre, 94275 Le Kremlin-Bicêtre, France; Institut National de la Santé et de la Recherche Médicale Unité 584, Hormone Targets, Faculté de Médecine Necker Enfants Malades, 75015 Paris, France; Institut National de la Santé et de la Recherche Médicale Unité 535, Génétique Epidémiologique et Structure des Populations Humaines, Hôpital de Bicêtre, 94275 Le Kremlin-Bicêtre...
- Hôpital Necker-Enfants Malades (FR)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2003-08-27
- Volume
- 100
- Issue
- 19
- Pages
- 10972-10976
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC196911
- OpenAlex
- W2143506157
- Cited by
- 2,431
- References
- 29
- Citations by year
- 2026: 36 · 2025: 65 · 2024: 99 · 2023: 78 · 2022: 123 · 2021: 115 · 2020: 130 · 2019: 120 · 2018: 144 · 2017: 121 · 2016: 127 · 2015: 133 · 2014: 137 · 2013: 147 · 2012: 153
- FWCI
- 45.57
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Keywords
- isolated hypogonadotropic hypogonadism, GPR54, loss-of-function mutations, chromosome 19p13, consanguineous family, GnRH receptor, orphan G protein-coupled receptor, gonadotropic axis, aberrant splicing, follicle-stimulating hormone, luteinizing hormone
- MeSH terms
- Receptors, Kisspeptin-1, Base Sequence, Consanguinity, Female, Genotype, Humans, Hypogonadism, Male, Pedigree, DNA Primers, Receptors, Neuropeptide, Receptors, G-Protein-Coupled
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
