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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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“Moreover, adult humans with mutations in the KISS1R gene, and mice with a targeted deletion of Kiss1r (Kiss1rKO), have undeveloped gonads, lack mature gametes, and have low-circulating gonadal steroid hormone levels [20–22].”
BackgroundG protein-coupled receptors involved in GnRH regulation: Molecular insights from human disease
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“Mutations in GPR54 cause autosomal recessive idiopathic hypogonadotropic hypogonadism in humans (Seminara et al., 2003; De Roux et al., 2003), whereas deletion of Grant sponsor: National Institutes of Health; Grant number: NS43330; Grant number: DK68098; Grant number: P30-NS061800.”
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“Targeted disruption of either ligand or receptor in animal models and mutations in human kiss-1/gpr54 genes lead to hypogonadotropic hypogonadism and lack of sexual maturation (d’Anglemont de Tassigny et al., 2007; De Roux et al., 2003; Seminara et al., 2003; Topaloglu et al., 2012).”
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“In humans, mutations of the KISS1 receptor (GPR54, more recently termed KISS1R) [4,6] and a recently described inactivating KISS1 mutation [7] lead to hypogonadotropic hypogonadism.”
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“Kisspeptin, also termed metastin, was discovered in 1996 [105] and became intimately associated with reproduction in 2003 when it was reported that mutations in the kisspeptin receptor, GPR54 (also known as Kiss1R), cause autosomal recessive idiopathic hypogonadism in humans, and deletion of GPR54 in mice results in d…”
BackgroundThe neuroendocrine physiology of kisspeptin in the human
Dhillo, W. S., Murphy, K. G., & Bloom, S. R. (2007) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-007-9029-1 · Cited by 44
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“has been recently identified as playing a pivotal role in the initiation of puberty [”
BackgroundCongenital hypogonadotropic hypogonadism in females: Clinical spectrum, evaluation and genetics
Bry‐Gauillard, H., Trabado, S., Bouligand, J., Sarfati, J., Francou, B., Salenave, S., Chanson, P., Brailly‐Tabard, S., Guiochon‐Mantel, A., & Young, J. (2010) · Annales d Endocrinologie · doi:10.1016/j.ando.2010.02.024 · Cited by 43
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Genetic Mechanisms Mediating Kisspeptin Regulation of GnRH gene Expression
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“Furthermore, inactivating mutations of the human GPR54 gene are linked to hypogonadotropic hypogonadism and an absence of puberty (de Roux et al., 2003; Seminara et al., 2003).”
BackgroundAfferent Neuronal Control of Type-I Gonadotropin Releasing Hormone Neurons in the Human
Hrabovszky, E., & Liposits, Z. (2013) · Frontiers in Endocrinology · doi:10.3389/fendo.2013.00130 · Cited by 44
“Kisspeptin signaling via its specific receptor (KISS1R) plays critically important roles in the regulation of puberty and reproduction.”
BackgroundInfluentialReproductive functions of kisspeptin and Gpr54 across the life cycle of mice and men
Chan, Y.-M., Broder‐Fingert, S., & Seminara, S. B. (2008) · Peptides · doi:10.1016/j.peptides.2008.06.015 · Cited by 45
“Mutations in GPR54 were initially reported by two groups studying families affected by idiopathic hypogonadotropic hypogonadism (IHH) [8,35].”
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Centrally administered kisspeptin suppresses feeding via nesfatin-1 and oxytocin in male rats
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“KP is a hypothalamic neuropeptide that drives fertility by stimulating gonadotropin-releasing hormone (GnRH) neurons, and puberty activation [6,7,12,13].”
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Kisspeptin Overcomes GnRH Neuronal Suppression Secondary to Hyperprolactinemia in Humans
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Targeted Disruption of ALK Reveals a Potential Role in Hypogonadotropic Hypogonadism
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Looking for the bird Kiss: evolutionary scenario in sauropsids
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“Whereas loss of function mutations in Kiss1r and KISS1R causes hypogonadotropic hypogonadism in mice and men (18-19), Kiss1r−/− mice permitted an examination of the hypothalamic content of GnRH which proved to be normal, leading to the hypothesis that kisspeptin does not affect GnRH neuronal fate specification, migrat…”
BackgroundInfluentialJayasena, C. N., Comninos, A. N., Nijher, G. M. K., Abbara, A., Silva, A. D., Veldhuis, J. D., Ratnasabapathy, R., Izzi‐Engbeaya, C. N., Lim, A. K. P., Patel, D., et al. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-1069 · Cited by 42
Kisspeptins and the control of gonadotrophin secretion
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“A homozygous 155 nucleotide deletion in the GPR54 receptor gene within the short arm of chromosome 19 (19p13) was the cause of the impaired GnRH stimulation and delayed puberty [de Roux et al. 2003].”
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The roles of kisspeptin in the mechanism underlying reproductive functions in mammals
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Physiology and Endocrinology of Puberty in Heifers
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“Human genetic studies demonstrated that kisspeptin (4) as well as neurokinin B (NKB) signaling (5) are”
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“[3] N.”
BackgroundKisspeptins and the neuroendocrine control of reproduction
Navarro, V. M. (2010) · Frontiers in Bioscience-Scholar · doi:10.2741/s150 · Cited by 42
“In recent years, our knowledge on reproductive endocrinology has experienced an unequivocal advance with the revolutionary discovery of the link between kisspeptins and reproductive function (2-4).”
Does Dynorphin Play a Role in the Onset of Puberty in Female Sheep?
Lopez, J. A., Bedenbaugh, M. N., McCosh, R. B., Weems, P. W., Meadows, L. J., Wisman, B. A., Coolen, L. M., Goodman, R. L., & Hileman, S. M. (2016) · Journal of Neuroendocrinology · doi:10.1111/jne.12445 · Cited by 41
GnRH in the Human Female Reproductive Axis
Limonta, P., Marelli, M. M., Moretti, R. M., Marzagalli, M., Fontana, F., & Maggi, R. (2018) · Vitamins and hormones · doi:10.1016/bs.vh.2018.01.003 · Cited by 41
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“In this regard, a mutation of GPR54 in humans, and a deletion of the GPR54 locus in mice, caused hypogonadotrophic hypogonadism and delayed puberty (de Roux et al. 2003; Seminera et al. 2003; Funes et al. 2003).”
BackgroundMittelman-Smith, M. A., Wong, A., Kathiresan, A. S. Q., & Micevych, P. E. (2015) · Endocrinology · doi:10.1210/en.2014-1803 · Cited by 39
Uenoyama, Y., Tsukamura, H., & Maeda, K. (2009) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2009.01853.x · Cited by 40
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Estradiol Membrane‐Initiated Signaling and Female Reproduction
Micevych, P. E., Wong, A., & Mittelman-Smith, M. A. (2015) · Comprehensive physiology · doi:10.1002/cphy.c140056 · Cited by 46
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“With one recent exception (see the following section), mutations in genes encoding neurotransmitter signalling systems have not been identified in humans with IHH. This may be because of the marked plasticity that exists within neuronal networks enabling specific molecules to be replaced without loss of function. GPR5…”
BackgroundHypothalamic Kisspeptin Neurons: Integral Elements of the GnRH System
Prashar, V., Arora, T., Singh, R., Sharma, A., & Parkash, J. (2022) · Reproductive Sciences · doi:10.1007/s43032-022-01027-5 · Cited by 46
“[22, 105] documented that deletion and inactivating mutations in the GPR54 gene result in defective gonadotropin secretion and infertility.”
BackgroundGenetic counseling for isolated GnRH deficiency
Au, M., Crowley, W. F., & Buck, C. L. (2011) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2011.05.041 · Cited by 40
“Rare variants in FGFR1 have also been associated with cleft lip/palate, syndactyly, brachydactyly, and agenesis of the corpus callosum (Dode et al., 2003; Pitteloud et al., 2006; Trarbach et al., 2006).”
Fatness rather than leptin sensitivity determines the timing of puberty in female mice
Bohlen, T. M., Silveira, M. A., Zampieri, T. T., Frazão, R., & Donato, J. (2016) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2015.12.022 · Cited by 40
Narayanaswamy, S., Prague, J., Jayasena, C. N., Papadopoulou, D., Mizamtsidi, M., Shah, A., Bassett, P., Comninos, A. N., Abbara, A., Bloom, S. R., et al. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-1911 · Cited by 39
“Mutations in the genes encoding for kisspeptin, NKB, and their receptors (KISS1, TAC3, KISS1R, TACR3) result in hypogonadotrophic hypogonadism (1, 2, 11), indicating that both kisspeptin and NKB are critical for normal GnRH secretion in humans and subsequent puberty and reproduction.”
BackgroundDNA Methylation Patterns in the Hypothalamus of Female Pubertal Goats
Chen, Y., Ye, J., Li, X., Gao, X., Zhang, K., Luo, L., Ding, J., Zhang, Y., Li, Y., Cao, H., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0165327 · Cited by 40
Physiology and Pathology of the Female Reproductive Axis
Bulun, S. E. (2011) · Elsevier eBooks · doi:10.1016/b978-1-4377-0324-5.00017-1 · Cited by 40
Kisspeptin enhances brain responses to olfactory and visual cues of attraction in men
Yang, L. Y., Demetriou, L., Wall, M. B., Mills, E., Zargaran, D., Sykes, M. C., Prague, J., Abbara, A., Owen, B. M., Bassett, P., et al. (2020) · JCI Insight · doi:10.1172/jci.insight.133633 · Cited by 41
Diet-Induced Hypothalamic Inflammation, Phoenixin, and Subsequent Precocious Puberty
Valsamakis, G., Arapaki, A., Balafoutas, D., Charmandari, E., & Vlahos, N. (2021) · Nutrients · doi:10.3390/nu13103460 · Cited by 40
“Interestingly, the crucial role of kisspeptin for puberty is proven, because inactivating mutations of the kisspeptin receptor results in patients who fail to progress through puberty [59,60].”
BackgroundAn ancient founder mutation in PROKR2 impairs human reproduction
Stefanija, M. A., Jeanpierre, M., Sykiotis, G. P., Young, J., Quinton, R., Abreu, A. P., Plummer, L., Au, M., Balasubramanian, R., Dwyer, A. A., et al. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds264 · Cited by 39
Chan, Y.-M., Lippincott, M. F., Butler, J. P., Sidhoum, V. F., Li, C. X., Plummer, L., & Seminara, S. B. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-2233 · Cited by 39
Interaction of Kisspeptin and the Somatotropic Axis
Whitlock, B. K., Daniel, J. A., Wilborn, R. R., Maxwell, H. S., Steele, B., & Sartin, J. L. (2010) · Neuroendocrinology · doi:10.1159/000318049 · Cited by 41
Role of the adipocyte-derived hormone leptin in reproductive control
García-Galiano, D., Allen, S. J., & Elias, C. F. (2014) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2014-0017 · Cited by 40
“In 2003, two independent studies reported that in humans and mice inactivating mutations of GPR54/Gpr54 gene are associated with hypogonadotropic hypogonadism [44, 45], and since then, a large number of labs have confirmed the major role of kisspeptin signaling in reproductive physiology [42, 46].”
BackgroundTerasaka, T., Otsuka, F., Tsukamoto, N., Nakamura, E., Inagaki, K., Toma, K., Ogura-Ochi, K., Glidewell-Kenney, C., Lawson, M. A., & Makino, H. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2013.07.009 · Cited by 41
Blasco, V., Pinto, F. M., Fernández‐Atutxa, A., Prados, N., Tena‐Sempere, M., Sánchez, M. F., & Candenas, L. (2018) · Journal of Assisted Reproduction and Genetics · doi:10.1007/s10815-018-1338-7 · Cited by 38
Pituitary Physiology and Diagnostic Evaluation
Kaiser, U. B., & Ho, K. K. Y. (2016) · Elsevier eBooks · doi:10.1016/b978-0-323-29738-7.00008-3 · Cited by 39
Yang, L.-K., Hou, Z.-S., & Tao, Y. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2020.165973 · Cited by 40
“KISS1R mutations—G protein-coupled receptor 54, GPR54 (encoded by KISS1R, also called kisspeptin receptor), and the cognate ligand, kisspeptin, are known as important regulators for gonadotropin-releasing hormone (GnRH) secretion [214, 215].”
BackgroundArcuate nucleus, median eminence, and hypophysial pars tuberalis
Korf, H., & Møller, M. (2021) · Handbook of clinical neurology · doi:10.1016/b978-0-12-820107-7.00015-x · Cited by 39
Stincic, T. L., Qiu, J., Connors, A. M., Kelly, M. J., & Rønnekleiv, O. K. (2021) · eNeuro · doi:10.1523/eneuro.0093-21.2021 · Cited by 40
“…century, it was discovered that that mutations in an orphan receptor GPR54 caused hypothalamic hypogonadism in humans, and deletion of GPR54 in mice resulted in defective sexual development and reproductive failure (De Roux et al., 2003; Seminara et al., 2003; d’Anglemont de Tassigny et al., 2007).”
BackgroundAdvances in clinical applications of kisspeptin-GnRH pathway in female reproduction
Hu, K.-L., Chen, Z., Li, X., Cai, E., Yang, H., Chen, Y., Wang, C., Ju, L., Deng, W., & Mu, L. (2022) · Reproductive Biology and Endocrinology · doi:10.1186/s12958-022-00953-y · Cited by 47
Ohga, H., Adachi, H., Matsumori, K., Kodama, R., Nyuji, M., Selvaraj, S., Kato, K., Yamamoto, S., Yamaguchi, A., & Matsuyama, M. (2014) · Comparative Biochemistry and Physiology Part A Molecular & Integrative Physiology · doi:10.1016/j.cbpa.2014.09.012 · Cited by 39
“Several reports of gene mutation in humans and mice revealed the “key” role of the kisspeptin receptor in reproductive functions (de Roux et al., 2003; Seminara et al., 2003).”
BackgroundKo, J. M., Lee, H. S., & Hwang, J. S. (2010) · Endocrine Journal · doi:10.1507/endocrj.k10e-073 · Cited by 38
Myers, M. A., Ebling, F. J. P., Nwagwu, M., Boulton, R., Wadhwa, K., Stewart, J., & KERR, J. B. (2005) · Journal of Anatomy · doi:10.1111/j.1469-7580.2005.00493.x · Cited by 39
“…disorders, gene mutations may disrupt migration of GnRHreleasing neurons (in Kallman’s syndrome), impair GnRH processing or prevent the secretion of GnRH, as in studies describing mutations of the GPR54 receptor (Franco et al. 1991; Jackson et al. 1997; de Roux et al. 2003; Seminara et al. 2003).”
ResultGreives, T. J., Kriegsfeld, L. J., Bentley, G. E., Tsutsui, K., & Demas, G. E. (2008) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.2008.0433 · Cited by 42
New insights in the genetics of isolated hypogonadotropic hypogonadism
Iovane, A., Aumas, C., & de Roux, N. (2004) · European Journal of Endocrinology · doi:10.1530/eje.0.151u083 · Cited by 40
Novel Insights into the Aetiology and Pathogenesis of Hypopituitarism
Dattani, M. (2004) · Hormone Research in Paediatrics · doi:10.1159/000080493 · Cited by 39
“A wide range of phenotypes has been described, from complete hypogonadism with undescended testes and presentation at birth to mild pubertal delay. Recently, a homozygous missense mutation was identified within a novel gene, GPR54 , in a highly consanguineous pedigree of patients with hypogonadotropic hypogonadism [”
BackgroundGöcz, B., Takács, S., Skrapits, K., Rumpler, É., Solymosi, N., Póliska, S., Colledge, W. H., Hrabovszky, E., & Sárvári, M. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.960769 · Cited by 36
“Inactivating mutations of KISS1R, which encodes the KiSS-1 receptor (1, 2) or KISS1 itself (3), cause hypogonadotropic hypogonadism in humans.”
BackgroundNiwczyk, O., Grymowicz, M., Szczęsnowicz, A., Hajbos, M., Kostrzak, A., Budzik, M. P., Maciejewska-Jeske, M., Bala, G., Smolarczyk, R., & Męczekalski, B. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24076840 · Cited by 39
Salmeri, N., Viganò, P., Cavoretto, P. I., Marci, R., & Candiani, M. (2023) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-023-09826-0 · Cited by 44
Fiorini, Z., & Jasoni, C. L. (2010) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2010.02059.x · Cited by 41
Puberty in Non-human Primates and Man
Plant, T. M., Terasawa, E., & Witchel, S. F. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-397175-3.00032-6 · Cited by 39
Saha, A., Pradhan, A., Sengupta, S., Nayak, M., Samanta, M., Sahoo, L., & Giri, S. S. (2015) · Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology · doi:10.1016/j.cbpb.2015.10.008 · Cited by 38
Kisspeptin expression in mouse Leydig cells correlates with age
Wang, J.-Y., Hsu, M.-C., Tseng, T.-H., Wu, L., Yang, K., & Chiu, C. (2015) · Journal of the Chinese Medical Association · doi:10.1016/j.jcma.2015.01.004 · Cited by 39
“Kisspeptin and its receptor, KISS1R, which is also known as G-protein-coupled receptor GPR54, regulate the secretion of GnRH from the hypothalamus and affect mammalian reproduction.(22,23) Mutations in Kiss1 or Kiss1r cause hypogonadotropic hypogonadism in mice and result in the reduced production of gonadotropins and…”
BackgroundMutations along the hypothalamic–pituitary–gonadal axis affecting male reproduction
Huhtaniemi, I. T., & Alevizaki, M. K. (2007) · Reproductive BioMedicine Online · doi:10.1016/s1472-6483(10)60529-9 · Cited by 39
Ando, H., Ogawa, S., Shahjahan, M., Ikegami, T., Doi, H., Hattori, A., & Parhar, I. S. (2014) · Journal of Neuroendocrinology · doi:10.1111/jne.12165 · Cited by 38
Sexual Precocity - Genetic Bases of Central Precocious Puberty and Autonomous Gonadal Activation
Macedo, D. B., Silveira, L. F. G., Bessa, D. D. S., Brito, V. N., & Latronico, A. C. (2015) · Endocrine development · doi:10.1159/000438874 · Cited by 40
An update on the genetic causes of central precocious puberty
Shin, Y. (2016) · Annals of Pediatric Endocrinology & Metabolism · doi:10.6065/apem.2016.21.2.66 · Cited by 40
Sato, K., Shirai, R., Hontani, M., Shinooka, R., Hasegawa, A., Kichise, T., Yamashita, T., Yoshizawa, H., Watanabe, R., Matsuyama, T., et al. (2017) · Journal of the American Heart Association · doi:10.1161/jaha.117.005790 · Cited by 40
“Both KPs and GPR54 are expressed in ECs, macrophages, cardiomyocytes, pancreas, hypothalamus, and extravillous trophoblast.(8,11,12,26) In our preliminary investigation (Data S1), both KP-10 and GPR54 are expressed at high levels in human coronary atherosclerotic lesions (Figure S2A).”
GLP-1 increases Kiss-1 mRNA expression in kisspeptin-expressing neuronal cells†
Oride, A., Kanasaki, H., Mijiddorj, T., Sukhbaatar, U., Hara, T., Tumurbaatar, T., & Kyo, S. (2017) · Biology of Reproduction · doi:10.1093/biolre/iox087 · Cited by 38
“A new concept of the HPG axis was established after the discovery of inactivating mutations in the kisspeptin receptor of patients with idiopathic hypogonadotropic hypogonadism [2, 3], and hypothalamic kisspeptin is currently understood to be located upstream of GnRH neurons and to govern the HPG axis [4, 5].”
BackgroundPolycystic ovary syndrome (PCOS) and kisspeptin – A Sri Lankan study
Umayal, B., Jayakody, S. P. M. B., Chandrasekharan, N., Wijesundera, W. S. S., & Wijeyaratne, C. N. (2018) · Journal of Postgraduate Medicine · doi:10.4103/jpgm.jpgm_683_17 · Cited by 38
ESR2 Is Essential for Gonadotropin-Induced Kiss1 Expression in Granulosa Cells
Chakravarthi, V. P., Khristi, V., Ghosh, S., Yerrathota, S., Dai, E., Roby, K. F., Wolfe, M. W., & Rumi, M. A. K. (2018) · Endocrinology · doi:10.1210/en.2018-00608 · Cited by 38
Special features of neuroendocrine interactions between stress and reproduction in teleosts
Rousseau, K., Prunet, P., & Dufour, S. (2020) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2020.113634 · Cited by 40
McCarthy, E. A., Dischino, D., Maguire, C., León, S., Talbi, R., Cheung, E., Schteingart, C. D., Rivière, P. J.-M., Reed, S. D., Steiner, R. A., et al. (2021) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgab602 · Cited by 41
Sivalingam, M., & Parhar, I. S. (2021) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2021.100951 · Cited by 40
“In late 2003, two reports emerged that presented the unsuspected role of dysregulated or loss of expression of KISS1R in the neuroendocrine control of reproduction, specifically the onset of puberty and hypogonadotropic hypogonadism (de Roux et al., 2003; Seminara et al., 2003).”
InfluentialNeely, E. K., & Crossen, S. S. (2014) · Current Opinion in Obstetrics & Gynecology · doi:10.1097/gco.0000000000000099 · Cited by 38
Precocious Puberty: Growth and Genetics
Phillip, M., & Lazar, L. (2005) · Hormone Research in Paediatrics · doi:10.1159/000087760 · Cited by 38
Weight-Adjusted Genome Scan Analysis for Mapping Quantitative Trait Loci for Menarchal Age
Rothenbühler, A., Fradin, D. D., Heath, S. C., Lefèvre, H., Bouvattier, C. M., Lathrop, M., & Bougneres, P. F. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-0150 · Cited by 38
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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