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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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BackgroundA role for kisspeptins in the regulation of gonadotropin secretion in the mouse
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Topaloglu, A. K., Reimann, F., Guclu, M., Yalin, A. S., Kotan, L. D., Porter, K. M., Serin, A., Mungan, N. O., Cook, J. R., Ozbek, M. N., et al. (2009) · Nature Genetics · doi:10.1038/ng.306 · Cited by 961
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“Certain forms of hypogonadotropic hypogonadism are caused by mutations in the G-protein-coupled receptor in both humans and in knockout mice [”
BackgroundBoehm, U., Bouloux, P.-M., Dattani, M. T., de Roux, N., Dodé, C., Dunkel, L., Dwyer, A. A., Giacobini, P., Hardelin, J.-P., Juul, A., et al. (2015) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2015.112 · Cited by 874
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“Pionneering studies (de Roux et al., 2003; Seminara et al., 2003) revealed that inactivating mutations in the G-coupled protein receptor 54 (GPR54, KiSS1r) resulted in idiopathic hypogonadotrophic hypogonadism, where the affected individuals did not undergo puberty.”
BackgroundIncreased hypothalamic GPR54 signaling: A potential mechanism for initiation of puberty in primates
Shahab, M., Mastronardi, C. A., Seminara, S. B., Crowley, W. F., Ojeda, S. R., & Plant, T. M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409822102 · Cited by 888
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“Studies in humans and mice have demonstrated the absolute necessity of GPR54 for puberty onset (7, 8), and administration of kisspeptin to juvenile rodents and primates activates gonadotropin secretion (9–11).”
BackgroundKisspeptin Signaling in the Brain
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“Various disabling mutations in KISS1R have been shown to occur in humans (23), and these mutations have involved deletion of as many as 155 nucleotides or as few as a single-nucleotide variant (L148S) in the second intracellular loop of the KISS1R gene (7, 24, 25).”
BackgroundKisspeptins and Reproduction: Physiological Roles and Regulatory Mechanisms
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“in patients with hypogonadotropic hypogonadism (95).”
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“Much of the recent focus on afferent control of GnRH secretion has been upon kisspeptin neurons located in the preoptic area (POA) and hypothalamus, based on the ability of mutations of the kisspeptin receptor to cause hypogonadotropic hypogonadism in humans and animal models (2, 3).”
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“In this context, the demonstration that inactivating mutations of their putative receptor led to reproductive failure due to hypogonadotropic hypogonadism highlighted a previously unsuspected role for the KiSS-1/ GPR54 system in the control of the gonadotropic axis (8, 9).”
BackgroundDifferential Regulation of KiSS-1 mRNA Expression by Sex Steroids in the Brain of the Male Mouse
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“Mutations of GPR54 prevent the onset of puberty in humans (11, 12) and mice (13).”
BackgroundControl of puberty in farmed fish
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The KiSS-1 receptor GPR54 is essential for the development of the murine reproductive system
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“In 2003, two independent groups identified ‘inactivating’ point mutations and deletions in KISS1R thatwereassociated with impaired pubertal development insome patients with hypogonadotropic hypogonadism (de Roux et al., 2003; Seminara et al., 2003).”
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“Two seminal clinical studies in 2003 identified kisspeptin and its receptor GPR54 to be essential for puberty onset and normal human fertility (de Roux et al., 2003; Seminara et al., 2003).”
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“Considering the proposed function of KiSS-1 in puberty onset (de Roux et al. 2003; Seminara et al. 2003; and the present results), we aimed at evaluating the potential interaction between leptin (as peripheral permissive signal) and KiSS-1 (as central triggering signal) in the acute regulation of…”
BackgroundInfluentialInactivating KISS1 Mutation and Hypogonadotropic Hypogonadism
Topaloglu, A. K., Tello, J. A., Kotan, L. D., Ozbek, M. N., Yilmaz, M. B., Erdogan, S., Gurbuz, F., Temiz, F., Millar, R. P., & Yuksel, B. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1111184 · Cited by 467
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“Recently the KiSS-1/GPR54 system has been pointed out as a relevant central regulator of the gonadotropic axis (13, 14).”
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Definition of the hypothalamic GnRH pulse generator in mice
Clarkson, J., Han, S. Y., Piet, R., McLennan, T., Kane, G. M., Ng, J., Porteous, R. W., Kim, J. S., Colledge, W. H., Iremonger, K. J., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1713897114 · Cited by 392
“Humans and rodents with global deletions or mutations in kisspeptin or the kisspeptin receptor fail to exhibit normal pulsatile luteinizing hormone (LH) secretion (9, 10, 12, 13).”
BackgroundSmith, J. T., Coolen, L. M., Kriegsfeld, L. J., Sari, I. P., Jaafarzadehshirazi, M. R., Maltby, M., Bateman, K., Goodman, R. L., Tilbrook, A. J., Ubuka, T., et al. (2008) · Endocrinology · doi:10.1210/en.2008-0581 · Cited by 387
“ductive axis and may be critical for the onset of puberty (12, 13).”
BackgroundNovel signals for the integration of energy balance and reproduction
Fernandez-Fernandez, R., Martini, A. C., Navarro, V. M., Castellano, J. M., Diéguez, C., Aguilar, E., Pinilla, L., & Tena‐Sempere, M. (2006) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2006.04.026 · Cited by 390
Digenic mutations account for variable phenotypes in idiopathic hypogonadotropic hypogonadism
Pitteloud, N., Quinton, R., Pearce, S., Raivio, T., Acierno, J., Dwyer, A., Plummer, L., Hughes, V., Seminara, S., Cheng, Y.-Z., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci29884 · Cited by 379
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., et al. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.5740-08.2009 · Cited by 379
“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).”
Rance, N. E., Dacks, P. A., Mittelman-Smith, M. A., Romanovsky, A. A., & Krajewski-Hall, S. J. (2013) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2013.07.003 · Cited by 380
“…women also express kisspeptin (Hrabovszky et al., 2010, 2011; Rometo et al., 2007), another essential peptide for puberty and reproduction (de Roux et al., 2003; Seminara et al., 2003; Topaloglu et al., 2012) and similar to NKB, kisspeptin mRNA is increased in postmenopausal women (Fig.”
BackgroundKelberman, D. (2006) · Journal of Clinical Investigation · doi:10.1172/jci28658 · Cited by 374
Lemko, H. M. D., Clifton, D. K., & Steiner, R. A. (2005) · Endocrinology · doi:10.1210/en.2005-1282 · Cited by 379
Hypothalamic pathways linking energy balance and reproduction
Hill, J. W., Elmquist, J. K., & Elias, C. F. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00670.2007 · Cited by 367
Oligogenic basis of isolated gonadotropin-releasing hormone deficiency
Sykiotis, G. P., Plummer, L., HUGHES, V. A., Au, M., Durrani, S., Nayak-Young, S., Dwyer, A. A., Quinton, R., Hall, J. E., Gusella, J. F., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1009622107 · Cited by 371
“Others, however, had single-allele variants in either KISS1R (9%) or GNRHR (6%) (Table S2), which are genes traditionally thought to underlie recessive isolated GnRH deficiency (23, 24, 26).”
BackgroundDonato, J., Cravo, R. M., Frazão, R., Gautron, L., Scott, M. M., Lachey, J. L., de Castro, I. A., Margatho, L. O., Lee, S., Lee, C., et al. (2010) · Journal of Clinical Investigation · doi:10.1172/jci45106 · Cited by 367
Herbison, A. E. (2008) · Brain Research Reviews · doi:10.1016/j.brainresrev.2007.05.006 · Cited by 351
Mutations of the KISS1 gene in disorders of puberty
Silveira, L. G., Noel, S. D., Silveira-Neto, A. P., Abreu, A. P., Brito, V. N., Santos, M. G., Bianco, S. D. C., Kuohung, W., Xu, S., Gryngarten, M., et al. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-2421 · Cited by 352
“Loss-of-function mutations of the kisspeptin receptor (GPR54 or KISS1R) cause normosmic IHH(9,10).”
BackgroundCharacterization of Kiss1 neurons using transgenic mouse models
Cravo, R. M., Margatho, L. O., Osborne-Lawrence, S., Donato, J., Atkin, S., Bookout, A. L., Rovinsky, S., Frazão, R., Lee, C. E., Gautron, L., et al. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2010.11.022 · Cited by 353
Steroidogenesis in the Fetal Testis and Its Susceptibility to Disruption by Exogenous Compounds
Scott, H. M., Mason, J. I., & Sharpe, R. M. (2009) · Endocrine Reviews · doi:10.1210/er.2009-0016 · Cited by 366
60 YEARS OF NEUROENDOCRINOLOGY: The hypothalamo-prolactin axis
Grattan, D. R. (2015) · Journal of Endocrinology · doi:10.1530/joe-15-0213 · Cited by 379
“Since first being identified as essential for puberty in humans (de Roux et al. 2003, Seminara et al. 2003), kisspeptin neurons are now recognised as critical parts of the circuit regulating activity of the GnRH neurons that control fertility (Pinilla et al. 2012).”
Distribution of Kisspeptin Neurones in the Adult Female Mouse Brain
Clarkson, J., D’Anglemont de Tassigny, X., Colledge, W. H., Caraty, A., & Herbison, A. E. (2009) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2009.01892.x · Cited by 346
“In humans, loss of function mutations of GPR54 result in failed puberty and infertility (1, 2 ), whereas gain of function mutations result in precocious puberty (3).”
BackgroundPielecka-Fortuna, J., Chu, Z., & Moenter, S. M. (2007) · Endocrinology · doi:10.1210/en.2007-1365 · Cited by 341
New frontiers in kisspeptin/GPR54 physiology as fundamental gatekeepers of reproductive function
Roa, J., Aguilar, E., Diéguez, C., Pinilla, L., & Tena‐Sempere, M. (2007) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2007.07.002 · Cited by 350
Mayer, C., Acosta‐Martínez, M., Dubois, S. L., Wolfe, A., Radovick, S., Boehm, U., & Levine, J. E. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1012406108 · Cited by 344
“Inactivating mutations of the human GPR54 gene are associated with hypogonadotropic hypogonadism and an absence of puberty (10, 11).”
BackgroundEnvironmental Factors and Puberty Timing: Expert Panel Research Needs
Louis, G. M. B., Gray, L. E., Marcus, M., Ojeda, S. R., Pescovitz, O. H., Witchel, S. F., Sippell, W. G., Abbott, D. H., Soto, A. M., Tyl, R. W., et al. (2008) · PEDIATRICS · doi:10.1542/peds.1813e · Cited by 334
The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism
Bianco, S. D. C., & Kaiser, U. B. (2009) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2009.177 · Cited by 336
“Regulation of GnRH secretion KISS1 and KISS1R 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…”
BackgroundMutant G-protein-coupled receptors as a cause of human diseases
Schöneberg, T., Schulz, A. M., Biebermann, H., Hermsdorf, T., Römpler, H., & Sangkuhl, K. (2004) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2004.08.008 · Cited by 343
The hypothalamus-pituitary-gonad axis: Tales of mice and men
Kaprara, A., & Huhtaniemi, I. T. (2017) · Metabolism · doi:10.1016/j.metabol.2017.11.018 · Cited by 346
Signaling by G-protein-coupled receptor (GPCR): Studies on the GnRH receptor
Naor, Z. (2008) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2008.07.001 · Cited by 333
“TGF-b and the Kisspeptin-GPR54 signaling in the brain is now recognized as an important conduit for controlling GnRH secretion in the developing and the adult animal [59,282,85,195,64].”
Parhar, I. S., Ogawa, S., & Sakuma, Y. (2004) · Endocrinology · doi:10.1210/en.2004-0395 · Cited by 324
The endocrine manifestations of anorexia nervosa: mechanisms and management
Haines, M. S., & Miller, K. K. (2016) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.175 · Cited by 342
Hrabovszky, E., Ciofi, P., Vida, B., Horvath, M. C., Keller, E., Caraty, A., Bloom, S. R., Ghatei, M. A., Dhillo, W. S., Liposits, Z., et al. (2010) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2010.07239.x · Cited by 314
“In humans, the loss-of-function mutations of the Kiss1R gene cause autosomal recessive hypogonadotropic hypogonadism (de Roux et al., 2003; Seminara et al., 2003; Semple et al., 2005), whereas activating mutation of Kiss1R results in central precocious puberty (Teles et al., 2008).”
BackgroundOjeda, S. R., Lomniczi, A., Mastronardi, C. A., Heger, S., Roth, C. L., Parent, A., Matagne, V., & Mungenast, A. E. (2005) · Endocrinology · doi:10.1210/en.2005-1136 · Cited by 320
“Metastin/ kisspeptin is a 53-amino acid peptide encoded by the KiSS1 gene (5, 6); proteolytic cleavage of the primary KiSS1 protein product originates the decapeptide kisspeptin-10, which is extraordinarily potent in eliciting LH release (36–38).”
BackgroundCaraty, A., Smith, J. T., Lomet, D., Ben Saïd, S., Morrissey, A., Cognie, J., Doughton, B., Baril, G., Briant, C., & Clarke, I. J. (2007) · Endocrinology · doi:10.1210/en.2007-0554 · Cited by 313
“The link between Kiss1/GPR54 and the reproductive system was made in two independent studies reporting that isolated hypogonadotropic hypogonadism in the human is associated with a genetic defect of the GPR54 gene (6, 7), and that a loss-of-function mutation of GPR54 gene in mice leads to a deficiency in sexual matura…”
BackgroundEpigenetic control of female puberty
Lomniczi, A., Loche, A., Castellano, J. M., Rønnekleiv, O. K., Bosch, M. A., Kaidar, G., Knoll, J. G., Wright, H., Pfeifer, G. P., & Ojeda, S. R. (2013) · Nature Neuroscience · doi:10.1038/nn.3319 · Cited by 318
Cheng, G., Coolen, L. M., Padmanabhan, V., Goodman, R. L., & Lehman, M. N. (2009) · Endocrinology · doi:10.1210/en.2009-0541 · Cited by 304
Navarro, V. M., Castellano, J. M., Fernández-Fernández, R., Tovar, S. A., Roa, J., Mayen, A., Barreiro, M. L., Casanueva, F. F., Aguilar, E., Diéguez, C., et al. (2005) · Endocrinology · doi:10.1210/en.2004-1353 · Cited by 317
Cloning and Expression of kiss2 in the Zebrafish and Medaka
Kitahashi, T., Ogawa, S., & Parhar, I. S. (2008) · Endocrinology · doi:10.1210/en.2008-0940 · Cited by 309
Plant, T. M., Ramaswamy, S., & DiPietro, M. J. (2005) · Endocrinology · doi:10.1210/en.2005-1261 · Cited by 298
Dhillo, W. S., Chaudhri, O. B., Thompson, E. L., Murphy, K. G., Patterson, M., Ramachandran, R., Nijher, G. M. K., Amber, V., Kokkinos, A. D., Donaldson, M., et al. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-1116 · Cited by 296
Gianetti, E., Tusset, C., Noel, S. D., Au, M. G., Dwyer, A. A., Hughes, V. A., Abreu, A. P., Carroll, J., Trarbach, E., Silveira, L. F. G., et al. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-2320 · Cited by 294
Semple, R. K., Achermann, J. C., Ellery, J., Farooqi, I. S., Karet, F. E., Stanhope, R. G., O’Rahilly, S., & Aparicio, S. A. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-1418 · Cited by 291
“or functional studies of this mutant were reported (4).”
BackgroundKisspeptin Mediates the Photoperiodic Control of Reproduction in Hamsters
Revel, F. G., Saboureau, M., Masson‐Pévet, M., Pévet, P., Mikkelsen, J. D., & Simonneaux, V. (2006) · Current Biology · doi:10.1016/j.cub.2006.07.025 · Cited by 299
Backholer, K., Smith, J. T., Rao, A. V. N., Pereira, A., Iqbal, J., Ogawa, S., Li, Q., & Clarke, I. J. (2010) · Endocrinology · doi:10.1210/en.2009-1190 · Cited by 299
“phenotype of metabolic disruption (69).”
60 YEARS OF NEUROENDOCRINOLOGY: The hypothalamo-pituitary–gonadal axis
Plant, T. M. (2015) · Journal of Endocrinology · doi:10.1530/joe-15-0113 · Cited by 289
Leptin in human physiology and therapeutics
Dardeno, T. A., Chou, S. H.-H., Moon, H., Chamberland, J. P., Fiorenza, C. G., & Mantzoros, C. S. (2010) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2010.06.002 · Cited by 297
“Mutations causing dysfunction of the kisspeptin receptor gene GPR54 result in hypogonadotrophic hypogonadism in both mice and humans [49,206], and in animals various kisspeptins have been shown to stimulate the release of GnRH and increase plasma levels of LH, follicule stimulating hormone (FSH), and total testosteron…”
Neuroendocrine Control of the Ovarian Cycle of the Rat
Freeman, M. R. (2006) · Elsevier eBooks · doi:10.1016/b978-012515400-0/50048-8 · Cited by 287
A Window of Opportunity: The Diagnosis of Gonadotropin Deficiency in the Male Infant 1
Grumbach, M. M. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-2465 · Cited by 281
Seasonal Regulation of Reproduction in Mammals
Hazlerigg, D. G., & Simonneaux, V. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-397175-3.00034-x · Cited by 288
Matsumoto, S.-I., Yamazaki, C., Masumoto, K.-H., Nagano, M., Naito, M., Soga, T., Hiyama, H., Matsumoto, M., Takasaki, J., Kamohara, M., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508881103 · Cited by 281
Ramaswamy, S., Guerriero, K. A., Gibbs, R. B., & Plant, T. M. (2008) · Endocrinology · doi:10.1210/en.2008-0438 · Cited by 279
“An important role for kisspeptin-GPR54 signaling in activating the pubertal increase in GnRH release emerged in 2003 when it was reported that several members of two large consanguineous families presenting with hypogonadotropic hypogonadism and absent puberty were found to carry homozygous loss of function mutations…”
BackgroundNeuro-toxic and Reproductive Effects of BPA
Santoro, A., Chianese, R., Troisi, J., Richards, S. M., Nori, S. L., Fasano, S., Guida, M., Plunk, E. C., Viggiano, A., Pierantoni, R., et al. (2019) · Current Neuropharmacology · doi:10.2174/1570159x17666190726112101 · Cited by 288
Tsutsui, K., Bentley, G. E., Bédécarrats, G. Y., Osugi, T., Ubuka, T., & Kriegsfeld, L. J. (2010) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2010.03.001 · Cited by 280
“Following the discovery of GnIH, kisspeptin, the peptide encoded by the KiSS-1 gene, was also discovered which plays an important role in the development and up-regulation of the reproductive system in mammals [21,29,83].”
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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