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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.
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“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]
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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
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
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“A role for the GPR54/KiSS-1 system recently emerged when two independent reports showed that mutations and deletions of the GPR54 gene were found in patients suffering from idiopathic hypogonadotropic hypogonadism [”
BackgroundLi, X. F., Knox, A. M. I., & O'Byrne, K. T. (2010) · Brain Research · doi:10.1016/j.brainres.2010.08.036 · Cited by 90
“The HPG axis is under the obligatory control of kisspeptin (Kiss1) and its receptor (Kiss1r), since mutations in the receptor results in hypogonadotrophic hypogonadism in humans and mice (de Roux et al., 2003; Seminara et al., 2003).”
BackgroundPrimary cilia enhance kisspeptin receptor signaling on gonadotropin-releasing hormone neurons
Koemeter-Cox, A., Sherwood, T. W., Green, J. A., Steiner, R. A., Berbari, N. F., Yoder, B. K., Kauffman, A. S., Monsma, P. C., Brown, A., Askwith, C. C., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1403286111 · Cited by 84
“One of these, the kisspeptin receptor (Kiss1r, also known as GPR54), was considered a strong candidate ciliary GPCR given that loss of Kiss1r leads to hypogonadotropic hypogonadism in humans and mice (16, 17) and hypogonadotropic hypogonadism is a feature of the ciliopathy Bardet-Biedl syndrome (18).”
BackgroundHypothalamic hamartoma with epilepsy: Review of endocrine comorbidity
Harrison, V. S., Oatman, O. J., & Kerrigan, J. (2017) · Epilepsia · doi:10.1111/epi.13756 · Cited by 89
“Loss of function mutations in the GPR54 gene were determined to be responsible for idiopathic hypogonadotropic hypogonadism in affected families.(34,35) Exogenous administration of kisspeptin to juvenile primates results in marked gonadotropin release.”
BackgroundHypothalamus as an Endocrine Organ
Clarke, I. J. (2014) · Comprehensive physiology · doi:10.1002/cphy.c140019 · Cited by 114
Sena, G. C., Freitas‐Lima, L. C., Merlo, E., Podratz, P. L., de Araújo, J. F. P., Brandão, P. A. A., Carneiro, M. T. W. D., Zicker, M. C., Ferreira, A. V. M., Takiya, C. M., et al. (2017) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2017.01.021 · Cited by 87
Kermath, B. A., & Gore, A. C. (2012) · Neuroendocrinology · doi:10.1159/000335994 · Cited by 87
Luan, X., Zhou, Y., Wang, W., Hong, Y., Pin, L., Gan, X., Wei, D., & Xiao, J. (2007) · European Journal of Endocrinology · doi:10.1530/eje-07-0061 · Cited by 86
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Smith, J. T., & Clarke, I. J. (2007) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-007-9026-4 · Cited by 90
Hagen, C. P., Sørensen, K., Mieritz, M. G., Johannsen, T. H., Almstrup, K., & Juul, A. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-4462 · Cited by 86
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“Thus, loss-of-function mutations in the kisspeptin receptor (GPR54) cause a failure to progress through puberty due to hypogonadotropic hypogonadism (58).”
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Patterson, M., Murphy, K. G., Thompson, E. L., Patel, S., Ghatei, M. A., & Bloom, S. R. (2006) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2006.01420.x · Cited by 86
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BackgroundWen, J., Liu, C., Bi, W., Hu, Y., Chen, Q., Huang, H., Liang, J., Li, L., Lin, L., & Chen, G. (2012) · Journal of Endocrinology · doi:10.1530/joe-12-0054 · Cited by 91
“…by the finding that inactivating mutations of the GPR54 gene were associated with the lack of puberty onset and hypogonadotropic hypogonadism both in humans and in mice (de Roux et al. 2003, Seminara et al. 2003), which indicates that KISS1 andGPR54 are the new gatekeepers of reproduction.”
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“Humans and rodents lacking either kisspeptin or its receptor, KISS1R, are completely infertile, with low LH and gonadal sex steroids due to diminished GnRH secretion (de Roux et al., 2003; Seminara et al., 2003; d’Anglemont de Tassigny et al., 2007; Lapatto et al., 2007; Topaloglu et al., 2012).”
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“Mutations in GNRH1, KISS1R and GNRHR genes cause ormosmic IHH, interfering with the normal synthesis, secretion or ction of GnRH, respectively (de Roux et al., 1997, 2003; Seminara t al., 2003; Bouligand et al., 2009; Chan et al., 2009).”
InfluentialMurine Arcuate Nucleus Kisspeptin Neurons Communicate with GnRH NeuronsIn Utero
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BackgroundTata, B. K., Huijbregts, L., Jacquier, S., Csaba, Z., Génin, E., Meyer, V., Leka, S., Dupont, J., Charles, P., Chevenne, D., et al. (2014) · PLoS Biology · doi:10.1371/journal.pbio.1001952 · Cited by 87
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“Kisspeptin neurons and the kisspeptin receptor The description of a patient with idiopathic hypogonadotropic hypogonadism with a mutation in the KISS1R, and a mouse model with a deletion of the Kiss1R gene added a new member to the axis structure (Seminara et al. 2003, de Roux et al. 2003).”
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“In 2003, GPR54 was implicated as an important regulator of puberty in both mice and humans (50-52).”
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“Following the discovery of GnIH, kisspeptin, the peptide products of the Kiss1 gene, was discovered in mammals [17] and other”
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“The discovery of kisspeptin secretion and its impact on the GnRH pulse generator was a major step in our understanding of the pubertal process (7, 8).”
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SHAHED, A. R., & Young, K. A. (2008) · Molecular Reproduction and Development · doi:10.1002/mrd.20972 · Cited by 84
“The important finding about the role of GPR54 receptor and its natural ligand KiSS-1 in the initiation of puberty via action on the hypothalamic- pituitary-gonadal (HPG) axis (de Roux et al. 2003; Seminara et al. 2003) has sparked great interest.”
BackgroundKisspeptin stimulation of insulin secretion: mechanisms of action in mouse islets and rats
Bowe, J. E., King, A., Kinsey‐Jones, J. S., Foot, V., Li, X. F., O’Byrne, K. T., Persaud, S. J., & Jones, P. M. (2009) · Diabetologia · doi:10.1007/s00125-009-1283-1 · Cited by 83
“The known involvement of kisspeptin in puberty [4, 5] and pregnancy [37, 38], and in mediating the effects of nutritional status on reproductive function [6, 7] raises the possibility that kisspeptin plays multiple roles as a physiological regulator of whole body fuel homeostasis, at least partly by regulating islet f…”
BackgroundLi, X. F., Lin, Y. S., Kinsey‐Jones, J. S., & O'Byrne, K. T. (2012) · Endocrinology · doi:10.1210/en.2012-1223 · Cited by 83
Roth, C. L., Mastronardi, C. A., Lomniczi, A., Wright, H., Cabrera, R., Mungenast, A. E., Heger, S., Jung, H., Dubay, C., & Ojeda, S. R. (2007) · Endocrinology · doi:10.1210/en.2007-0634 · Cited by 83
“The importance of TRGs in the control of the pubertal process was hinted by the loss of SynCAM1 expression in mice with delayed puberty (52) and made evident by the critical importance of the KiSS1/GPR54 signaling system in the control of human, nonhuman primate, and rodent puberty (2, 3, 21) (reviewed in Ref.”
BackgroundSex hormone–binding globulin: biomarker and hepatokine?
Simons, P. I. H. G., Valkenburg, O., Stehouwer, C. D. A., & Brouwers, M. C. G. J. (2021) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2021.05.002 · Cited by 82
Uenoyama, Y., Inoue, N., Nakamura, S., & Tsukamura, H. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179229 · Cited by 85
“In 2003, two independent research groups reported that inactivating mutations in the GPR54 gene caused hypogonadotropic hypogonadism in humans [65,66].”
BackgroundKisspeptin modulates fertilization capacity of mouse spermatozoa
Hsu, M.-C., Wang, J.-Y., Lee, Y., Jong, D., Tsui, K., & Chiu, C. (2014) · Reproduction · doi:10.1530/rep-13-0368 · Cited by 82
“Kisspeptins and the kisspeptin receptor KISS1R (also known as the G protein-coupled receptor 54) play key roles in mammalian reproduction by regulating gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus (de Roux et al. 2003, Seminara et al. 2003).”
BackgroundKisspeptin activates the hypothalamic–adenohypophyseal–gonadal axis in prepubertal ewe lambs
Redmond, J. S., Macedo, G. G., Velez, I. C., Caraty, A., Williams, G. L., & Amstalden, M. (2011) · Reproduction · doi:10.1530/rep-10-0467 · Cited by 81
“Kisspeptin (d’Anglemont de Tassigny et al. 2007, Lapatto et al. 2007) and its receptor (de Roux et al. 2003, Seminara q 2011 Society for Reproduction and Fertility ISSN 1470–1626 (paper) 1741–7899 (online) et al. 2003) are essential for normal onset of puberty.”
BackgroundHu, M., Li, X. F., McCausland, B., Li, S. Y., Gresham, R., Kinsey‐Jones, J. S., Gardiner, J., Sam, A. H., Bloom, S. R., Poston, L., et al. (2015) · Endocrinology · doi:10.1210/en.2014-1655 · Cited by 80
“Kisspeptin (Kiss1) is essential for sexual maturation because inactivating mutations in Kiss1 (1) or its receptor (Kiss1r) (2, 3) result in a lack of puberty and hypogonadotropic hypogonadism, and activating mutations cause precocious puberty (4, 5).”
BackgroundDeciphering Genetic Disease in the Genomic Era: The Model of GnRH Deficiency
Sykiotis, G. P., Pitteloud, N., Seminara, S. B., Kaiser, U. B., & Crowley, W. F. (2010) · Science Translational Medicine · doi:10.1126/scitranslmed.3000288 · Cited by 80
“KAL1, Kallmann syndrome 1 sequence, MIM: 308700; FGFR1, fibroblast growth factor receptor 1, MIM: 136350; FGF8, fibroblast growth factor 8, MIM: 600483; PROKR2, prokineticin receptor 2, MIM: 607123; PROK2, prokineticin 2, MIM: 607002; CHD7, chromodomain helicase DNA binding protein 7, MIM: 608765; NELF, nasal embryoni…”
BackgroundInfluentialSobrino, V., Avendaño, M. S., Perdices-López, C., Jiménez-Puyer, M., & Tena‐Sempere, M. (2022) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2021.100977 · Cited by 86
“Disclosure of their reproductive dimension came in late 2003, when two seminal publications reported in a lapse of few weeks that inactivating mutations in humans and rodents affecting Gpr54 caused hypogonadism of central origin [8; 9].”
Distribution of 26RFa binding sites and GPR103 mRNA in the central nervous system of the rat
Bruzzone, F., Lectez, B. L. P., Alexandre, D., Jégou, S., Mounien, L., Tollemer, H., Chatenet, D., Leprince, J., Vallarino, M., Vaudry, H., et al. (2007) · The Journal of Comparative Neurology · doi:10.1002/cne.21400 · Cited by 85
Postnatal and Pubertal Development of the Rhesus Monkey (Macaca mulatta) Testis
Plant, T. M., Ramaswamy, S., Simorangkir, D. R., & Marshall, G. R. (2005) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1336.016 · Cited by 79
Hrabovszky, E. (2011) · Frontiers in Endocrinology · doi:10.3389/fendo.2011.00080 · Cited by 80
“Loss-of-function mutations of the genes encoding kisspeptin receptor (KISS1R; de Roux et al., 2003; Seminara et al., 2003; Semple et al., 2005), NKB (Topaloglu et al., 2009), or the receptor for NKB (NK3; Guran et al., 2009; Topaloglu et al., 2009) cause hypogonadotropic hypogonadism in the human.”
BackgroundOhkura, S., Uenoyama, Y., Yamada, S., Homma, T., Takase, K., Inoue, N., Maeda, K.-I., & Tsukamura, H. (2009) · Peptides · doi:10.1016/j.peptides.2008.08.004 · Cited by 80
Stathatos, N., Bourdeau, I., Espinosa, A. V., Saji, M., Vasko, V. V., Burman, K. D., Stratakis, C. A., & Ringel, M. D. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-0963 · Cited by 81
GPCRs: The most promiscuous druggable receptor of the mankind
Alhosaini, K. A., Azhar, A., Alonazi, A. S., & Al-Zoghaibi, F. (2021) · Saudi Pharmaceutical Journal · doi:10.1016/j.jsps.2021.04.015 · Cited by 86
“Another example of receptor function attenuation is a mutation in the gonadotropin-releasing hormone receptor (GNRHR) in the GPR54 gene, inducing loss of receptor function (de Roux et al., 2003).”
Fraser, G. L., Hoveyda, H. R., Clarke, I. J., Ramaswamy, S., Plant, T. M., Rose, C., & Millar, R. P. (2015) · Endocrinology · doi:10.1210/en.2015-1409 · Cited by 79
“ceptor 54) receptors (5, 6), however, a loss-of function”
BackgroundCalder, M. D., Chan, Y.-M., Raj, R. S., Pampillo, M., Elbert, A., Noonan, M. M., Gillio‐Meina, C., Caligioni, C. S., Bérubé, N. G., Bhattacharya, M. M., et al. (2014) · Endocrinology · doi:10.1210/en.2013-1916 · Cited by 82
Genetic aspects of female reproduction
The ESHRE Capri Workshop Group (2008) · Human Reproduction Update · doi:10.1093/humupd/dmn009 · Cited by 81
Quillet, R., Ayachi, S., Bihel, F. J. ‐., Elhabazi, K., Ilien, B., & Simonin, F. (2016) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2016.02.005 · Cited by 84
Neuroanatomical Framework of the Metabolic Control of Reproduction
Hill, J. W., & Elias, C. F. (2018) · Physiological Reviews · doi:10.1152/physrev.00033.2017 · Cited by 80
“Loss-of-function mutations in KISS1/Kiss1 or kisspeptin receptor (GPR54/Gpr54, also known as Kiss1r) genes cause infertility in humans and mice due to a lack of pubertal development and hypogonadotropic hypogonadism (107, 119, 262, 408, 450).”
BackgroundEtiology and Treatment of Hypogonadism in Adolescents
Viswanathan, V., & Eugster, E. A. (2011) · Pediatric Clinics of North America · doi:10.1016/j.pcl.2011.07.009 · Cited by 79
“Another important cause of IHH has been traced to mutations in GPR54, which has a critical role in hypothalamic GnRH signaling and release.(20) Of note, both KS and IHH may be found in the same kindred.”
BackgroundDror, T. W., Franks, J., & Kauffman, A. S. (2013) · Biology of Reproduction · doi:10.1095/biolreprod.113.108555 · Cited by 81
The Role of Kisspeptin in Female Reproduction
Nejad, S. Z., Tehrani, F. R., & Zadeh–Vakili, A. (2017) · Intern J Endocrinol Metab · doi:10.5812/ijem.44337 · Cited by 81
“In 2003, inactivating mutations of the GPR54 were found in individuals with hypogonadotropic hypogonadism (13-15).”
BackgroundInfluentialLi, J., & Ge, W. (2020) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2020.110778 · Cited by 84
Neuropeptide co-expression in hypothalamic kisspeptin neurons of laboratory animals and the human
Skrapits, K., Borsay, B. Á., Herczeg, L., Ciofi, P., Liposits, Z., & Hrabovszky, E. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00029 · Cited by 79
“Inactivating mutations of the genes encoding for KP (KISS1) (Topaloglu et al., 2012) or its G-protein-coupled receptor (KISS1R; previously called GPR-54) (De Roux et al., 2003; Seminara et al., 2003) cause hypogonadotropic hypogonadism in humans.”
BackgroundMechanisms of Disease: mutations of G proteins and G-protein-coupled receptors in endocrine diseases
Lania, A. G., Mantovani, G., & Spada, A. (2006) · Nature Clinical Practice Endocrinology & Metabolism · doi:10.1038/ncpendmet0324 · Cited by 78
“Loss-of-function KiSS-1R mutations cause congenital hypogonadotropic hypogonadism in both sexes, characterized by delayed puberty, low sex steroid levels, and low-normal gonadotropin levels that are responsive to GnRH”
BackgroundPreweaning Over- and Underfeeding Alters Onset of Puberty in the Rat Without Affecting Kisspeptin1
Smith, J. T., & Spencer, S. J. (2012) · Biology of Reproduction · doi:10.1095/biolreprod.111.097758 · Cited by 78
Prévot, V. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-397175-3.00030-2 · Cited by 79
Skorupskaite, K., George, J. T., Veldhuis, J. D., Millar, R. P., & Anderson, R. A. (2017) · Neuroendocrinology · doi:10.1159/000473893 · Cited by 79
The Emerging Role(s) for Kisspeptin in Metabolism in Mammals
Wolfe, A., & Hussain, M. A. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00184 · Cited by 83
“While the kisspeptin gene and its activation of the kisspeptin receptor (KISS1R) were initially characterized by cancer biologists (1, 2), in 2003, the study of kisspeptin accelerated following the demonstration by two groups of its essential role in regulating reproductive function (3, 4).”
BackgroundNew Causes of Central Precocious Puberty: The Role of Genetic Factors
Macedo, D. B., Brito, V. N., & Latronico, A. C. (2014) · Neuroendocrinology · doi:10.1159/000366282 · Cited by 80
Kisspeptin and GnRH interactions in the reproductive brain of teleosts
Somoza, G. M., Mechaly, A. S., & Trudeau, V. L. (2020) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2020.113568 · Cited by 77
Comparison of the effects of peripherally administered kisspeptins
Mikkelsen, J. D., Overgaard, A., Ansel-Bollepalli, L., Simonneaux, V., & Juul, A. (2008) · Regulatory Peptides · doi:10.1016/j.regpep.2008.10.001 · Cited by 81
Csabafi, K., Jászberényi, M., Bagosi, Z., Lipták, N., & Telegdy, G. (2012) · Behavioural Brain Research · doi:10.1016/j.bbr.2012.11.039 · Cited by 79
Clinical genetics of Kallmann syndrome
Dodé, C., & Hardelin, J. (2010) · Annales d Endocrinologie · doi:10.1016/j.ando.2010.02.005 · Cited by 82
Regulation and Disorders of Pubertal Timing
Nathan, B. M., & Palmert, M. R. (2005) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2005.04.015 · Cited by 75
“The recent finding that mutations in GPR54, a G protein-coupled receptor, cause HH [48,49] identifies an important new pathway that regulates GnRH secretion.”
BackgroundYeo, S.-H., & Colledge, W. H. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00188 · Cited by 76
“Suppressive effect of dynorphin(1-13) on luteinizing hormone release in conscious castrated rats.”
BackgroundPoling, M. C., & Kauffman, A. S. (2011) · Endocrinology · doi:10.1210/en.2011-1838 · Cited by 76
ENDOCRINOLOGY AND ADOLESCENCE: Deciphering puberty: novel partners, novel mechanisms
Tena‐Sempere, M. (2012) · European Journal of Endocrinology · doi:10.1530/eje-12-0669 · Cited by 76
Ontogeny of Hypothalamus-Pituitary Gonadal Axis and Minipuberty: An Ongoing Debate?
Bizzarri, C., & Cappa, M. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00187 · Cited by 86
Son, Y. L., Ubuka, T., & Tsutsui, K. (2021) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2021.100953 · Cited by 81
Bianco, S. D. C., Vandepas, L. E., Correa-Medina, M., Gereben, B., Mukherjee, A., Kuohung, W., Carroll, R. S., Teles, M. G., Latronico, A. C., & Kaiser, U. B. (2011) · Endocrinology · doi:10.1210/en.2010-0903 · Cited by 78
Lin, L., Conway, G. S., Hill, N. R., Dattani, M., Hindmarsh, P. C., & Achermann, J. C. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-0807 · Cited by 76
Quaynor, S. D., Hu, L., Leung, P. K., Feng, H., Mores, N., Krsmanović, L. Z., & Catt, K. J. (2007) · Molecular Endocrinology · doi:10.1210/me.2007-0207 · Cited by 75
Targeted mutation of secretogranin-2 disrupts sexual behavior and reproduction in zebrafish
Mitchell, K., Zhang, W. S., Lu, C., Tao, B., Chen, L., Hu, W., & Trudeau, V. L. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2002004117 · Cited by 73
“There were no significant main effects of genotype [F(1) = 0.”
BackgroundInfluentialFunction-related structural plasticity of the GnRH system
Prévot, V., Hanchate, N. K., Bellefontaine, N., Sharif, A., Parkash, J., Estrella, C., Allet, C., Seranno, S. D., Campagne, C., de Tassigny, X. D., et al. (2010) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2010.05.003 · Cited by 82
Foster, D. L., & Hileman, S. M. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-397175-3.00031-4 · Cited by 76
Kisspeptin signaling in the brain: Recent developments and future challenges
Tena‐Sempere, M. (2009) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2009.05.004 · Cited by 75
“A major twist in this field, however, took place in late 2003, when humans and mice with genetic inactivation of GPR54/KISS1R were found to suffer hypogonadotropic hypogonadism [5,6].”
Cerrato, F. E., Shagoury, J. K., Králíčková, M., Dwyer, A. A., Falardeau, J. L., Özata, M., Vliet, G. V., Bouloux, P. M., Hall, J. E., Hayes, F. J., et al. (2006) · European Journal of Endocrinology · doi:10.1530/eje.1.02235 · Cited by 73
Smarr, B. L., Morris, E. L., & de la Iglesia, H. O. (2012) · Endocrinology · doi:10.1210/en.2011-1857 · Cited by 75
Bellefontaine, N., Hanchate, N. K., Parkash, J., Campagne, C., Seranno, S. D., Clasadonte, J., de Tassigny, X. D., & Prévot, V. (2011) · Neuroendocrinology · doi:10.1159/000324147 · Cited by 75
GPR54 and rGnRH I gene expression during the onset of puberty in Nile tilapia
Martínez‐Chávez, C. C., Minghetti, M., & Migaud, H. (2008) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2008.01.019 · Cited by 74
Dhillo, W. S., Savage, P. M., Murphy, K. G., Chaudhri, O. B., Patterson, M., Nijher, G. M. K., Foggo, V., Dancey, G. S., Mitchell, H., Seckl, M. J., et al. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00555.2005 · Cited by 76
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
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