ArticleThe Journal of clinical endocrinology and metabolism2009
Hypogonadotropic hypogonadism due to a novel missense mutation in the first extracellular loop of the neurokinin B receptor.
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Article in The Journal of clinical endocrinology and metabolism, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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57citing papers in PubMed
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Who cites it
57 citing papers in PubMed, 135 citations in OpenAlex.
- Effects of neurokinin B administration on reproductive hormone secretion in healthy men and women.The Journal of clinical endocrinology and metabolism · 2014Trial
- Identifying selection signatures for immune response and resilience to Aleutian disease in mink using genotype data.Frontiers in genetics · 2024Article
- Neurokinin B Administration Induces Dose Dependent Proliferation of Seminal Vesicles in Adult Rats.Current protein & peptide science · 2024Article
- Hypothalamic Kisspeptin Neurons: Integral Elements of the GnRH System.Reproductive sciences (Thousand Oaks, Calif.) · 2023Review
- Tachykinin receptor 3 in the lateral habenula alleviates pain and anxiety comorbidity in mice.Frontiers in immunology · 2023Article
- Functional Rescue of Inactivating Mutations of the Human Neurokinin 3 Receptor Using Pharmacological Chaperones.International journal of molecular sciences · 2022Article
- The Role of Kisspeptin in the Control of the Hypothalamic-Pituitary-Gonadal Axis and Reproduction.Frontiers in endocrinology · 2022Review
- Genetic architecture of self-limited delayed puberty and congenital hypogonadotropic hypogonadism.Frontiers in endocrinology · 2022Review
- Tachykinins, new players in the control of reproduction and food intake: A comparative review in mammals and teleosts.Frontiers in endocrinology · 2022Review
- Kisspeptin, Neurokinin B, and Dynorphin Expression during Pubertal Development in Female Sheep.Biology · 2021Article
- Role of KNDy Neurons Expressing Kisspeptin, Neurokinin B, and Dynorphin A as a GnRH Pulse Generator Controlling Mammalian Reproduction.Frontiers in endocrinology · 2021Review
- Genetic Evaluation of Patients With Delayed Puberty and Congenital Hypogonadotropic Hypogonadism: Is it Worthy of Consideration?Frontiers in endocrinology · 2020Review
- AGenes · 2019Article
- Delayed Puberty-Phenotypic Diversity, Molecular Genetic Mechanisms, and Recent Discoveries.Endocrine reviews · 2019Review
- Article
- A novel stopgain mutation c.G992A (p.W331X) in TACR3 gene was identified in nonobstructive azoospermia by targeted next-generation sequencing.Journal of clinical laboratory analysis · 2019Article
- Central Mechanism Controlling Pubertal Onset in Mammals: A Triggering Role of Kisspeptin.Frontiers in endocrinology · 2019Review
- NK3R Mediates the EGF-Induced SLα Secretion and mRNA Expression in Grass Carp Pituitary.International journal of molecular sciences · 2018Article
- The possible effects of anthropogenic acoustic pollution on marine mammals' reproduction: an emerging threat to animal extinction.Environmental science and pollution research international · 2018Review
- Alcohol Delays the Onset of Puberty in the Female Rat by Altering Key Hypothalamic Events.Alcoholism, clinical and experimental research · 2018Article
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Authors and funding
16 authors at 4 institutions in 2 countries.
Tulay Guran *Pediatric Endocrinology (T.G., A.B., S.T., T.A., Z.A.), Marmara University Hospital, Altunizade, 34662 Istanbul, Turkey; University of Cambridge (F.R., F.M.G., G.T.), Department of Clinical Biochemistry, Addenbrooke's Hospital, Cambridge CB2 8RP, United Kingdom; University of Cambridge Metabolic Research Laboratories (N.R., K.P., S.O., R.K.S.), Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 8RP, United Kingdom; Forensic Medicine (L.D.K., H.C., A.S.), Cukurova University, Faculty of Medicine, Balcali, 01330 Adana, Turkey; and Pediatric Endocrinology and Metabolism (A.K.T.), Cukurova University, Faculty of Medicine, Balcali, 01330 Adana, Turkey.
Gwen Tolhurst *Pediatric Endocrinology (T.G., A.B., S.T., T.A., Z.A.), Marmara University Hospital, Altunizade, 34662 Istanbul, Turkey; University of Cambridge (F.R., F.M.G., G.T.), Department of Clinical Biochemistry, Addenbrooke's Hospital, Cambridge CB2 8RP, United Kingdom; University of Cambridge Metabolic Research Laboratories (N.R., K.P., S.O., R.K.S.), Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 8RP, United Kingdom; Forensic Medicine (L.D.K., H.C., A.S.), Cukurova University, Faculty of Medicine, Balcali, 01330 Adana, Turkey; and Pediatric Endocrinology and Metabolism (A.K.T.), Cukurova University, Faculty of Medicine, Balcali, 01330 Adana, Turkey.
Abdullah BereketPediatric Endocrinology (T.G., A.B., S.T., T.A., Z.A.), Marmara University Hospital, Altunizade, 34662 Istanbul, Turkey; University of Cambridge (F.R., F.M.G., G.T.), Department of Clinical Biochemistry, Addenbrooke's Hospital, Cambridge CB2 8RP, United Kingdom; University of Cambridge Metabolic Research Laboratories (N.R., K.P., S.O., R.K.S.), Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 8RP, United Kingdom; Forensic Medicine (L.D.K., H.C., A.S.), Cukurova University, Faculty of Medicine, Balcali, 01330 Adana, Turkey; and Pediatric Endocrinology and Metabolism (A.K.T.), Cukurova University, Faculty of Medicine, Balcali, 01330 Adana, Turkey.
Nuno RochaPediatric Endocrinology (T.G., A.B., S.T., T.A., Z.A.), Marmara University Hospital, Altunizade, 34662 Istanbul, Turkey; University of Cambridge (F.R., F.M.G., G.T.), Department of Clinical Biochemistry, Addenbrooke's Hospital, Cambridge CB2 8RP, United Kingdom; University of Cambridge Metabolic Research Laboratories (N.R., K.P., S.O., R.K.S.), Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 8RP, United Kingdom; Forensic Medicine (L.D.K., H.C., A.S.), Cukurova University, Faculty of Medicine, Balcali, 01330 Adana, Turkey; and Pediatric Endocrinology and Metabolism (A.K.T.), Cukurova University, Faculty of Medicine, Balcali, 01330 Adana, Turkey.
Keith PorterPediatric Endocrinology (T.G., A.B., S.T., T.A., Z.A.), Marmara University Hospital, Altunizade, 34662 Istanbul, Turkey; University of Cambridge (F.R., F.M.G., G.T.), Department of Clinical Biochemistry, Addenbrooke's Hospital, Cambridge CB2 8RP, United Kingdom; University of Cambridge Metabolic Research Laboratories (N.R., K.P., S.O., R.K.S.), Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 8RP, United Kingdom; Forensic Medicine (L.D.K., H.C., A.S.), Cukurova University, Faculty of Medicine, Balcali, 01330 Adana, Turkey; and Pediatric Endocrinology and Metabolism (A.K.T.), Cukurova University, Faculty of Medicine, Balcali, 01330 Adana, Turkey.
Serap TuranPediatric Endocrinology (T.G., A.B., S.T., T.A., Z.A.), Marmara University Hospital, Altunizade, 34662 Istanbul, Turkey; University of Cambridge (F.R., F.M.G., G.T.), Department of Clinical Biochemistry, Addenbrooke's Hospital, Cambridge CB2 8RP, United Kingdom; University of Cambridge Metabolic Research Laboratories (N.R., K.P., S.O., R.K.S.), Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 8RP, United Kingdom; Forensic Medicine (L.D.K., H.C., A.S.), Cukurova University, Faculty of Medicine, Balcali, 01330 Adana, Turkey; and Pediatric Endocrinology and Metabolism (A.K.T.), Cukurova University, Faculty of Medicine, Balcali, 01330 Adana, Turkey.
Fiona M GribblePediatric Endocrinology (T.G., A.B., S.T., T.A., Z.A.), Marmara University Hospital, Altunizade, 34662 Istanbul, Turkey; University of Cambridge (F.R., F.M.G., G.T.), Department of Clinical Biochemistry, Addenbrooke's Hospital, Cambridge CB2 8RP, United Kingdom; University of Cambridge Metabolic Research Laboratories (N.R., K.P., S.O., R.K.S.), Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 8RP, United Kingdom; Forensic Medicine (L.D.K., H.C., A.S.), Cukurova University, Faculty of Medicine, Balcali, 01330 Adana, Turkey; and Pediatric Endocrinology and Metabolism (A.K.T.), Cukurova University, Faculty of Medicine, Balcali, 01330 Adana, Turkey.
L Damla KotanPediatric Endocrinology (T.G., A.B., S.T., T.A., Z.A.), Marmara University Hospital, Altunizade, 34662 Istanbul, Turkey; University of Cambridge (F.R., F.M.G., G.T.), Department of Clinical Biochemistry, Addenbrooke's Hospital, Cambridge CB2 8RP, United Kingdom; University of Cambridge Metabolic Research Laboratories (N.R., K.P., S.O., R.K.S.), Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 8RP, United Kingdom; Forensic Medicine (L.D.K., H.C., A.S.), Cukurova University, Faculty of Medicine, Balcali, 01330 Adana, Turkey; and Pediatric Endocrinology and Metabolism (A.K.T.), Cukurova University, Faculty of Medicine, Balcali, 01330 Adana, Turkey.
Teoman AkcayPediatric Endocrinology (T.G., A.B., S.T., T.A., Z.A.), Marmara University Hospital, Altunizade, 34662 Istanbul, Turkey; University of Cambridge (F.R., F.M.G., G.T.), Department of Clinical Biochemistry, Addenbrooke's Hospital, Cambridge CB2 8RP, United Kingdom; University of Cambridge Metabolic Research Laboratories (N.R., K.P., S.O., R.K.S.), Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 8RP, United Kingdom; Forensic Medicine (L.D.K., H.C., A.S.), Cukurova University, Faculty of Medicine, Balcali, 01330 Adana, Turkey; and Pediatric Endocrinology and Metabolism (A.K.T.), Cukurova University, Faculty of Medicine, Balcali, 01330 Adana, Turkey.
Zeynep AtayPediatric Endocrinology (T.G., A.B., S.T., T.A., Z.A.), Marmara University Hospital, Altunizade, 34662 Istanbul, Turkey; University of Cambridge (F.R., F.M.G., G.T.), Department of Clinical Biochemistry, Addenbrooke's Hospital, Cambridge CB2 8RP, United Kingdom; University of Cambridge Metabolic Research Laboratories (N.R., K.P., S.O., R.K.S.), Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 8RP, United Kingdom; Forensic Medicine (L.D.K., H.C., A.S.), Cukurova University, Faculty of Medicine, Balcali, 01330 Adana, Turkey; and Pediatric Endocrinology and Metabolism (A.K.T.), Cukurova University, Faculty of Medicine, Balcali, 01330 Adana, Turkey.
Husniye CananPediatric Endocrinology (T.G., A.B., S.T., T.A., Z.A.), Marmara University Hospital, Altunizade, 34662 Istanbul, Turkey; University of Cambridge (F.R., F.M.G., G.T.), Department of Clinical Biochemistry, Addenbrooke's Hospital, Cambridge CB2 8RP, United Kingdom; University of Cambridge Metabolic Research Laboratories (N.R., K.P., S.O., R.K.S.), Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 8RP, United Kingdom; Forensic Medicine (L.D.K., H.C., A.S.), Cukurova University, Faculty of Medicine, Balcali, 01330 Adana, Turkey; and Pediatric Endocrinology and Metabolism (A.K.T.), Cukurova University, Faculty of Medicine, Balcali, 01330 Adana, Turkey.
Ayse SerinPediatric Endocrinology (T.G., A.B., S.T., T.A., Z.A.), Marmara University Hospital, Altunizade, 34662 Istanbul, Turkey; University of Cambridge (F.R., F.M.G., G.T.), Department of Clinical Biochemistry, Addenbrooke's Hospital, Cambridge CB2 8RP, United Kingdom; University of Cambridge Metabolic Research Laboratories (N.R., K.P., S.O., R.K.S.), Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 8RP, United Kingdom; Forensic Medicine (L.D.K., H.C., A.S.), Cukurova University, Faculty of Medicine, Balcali, 01330 Adana, Turkey; and Pediatric Endocrinology and Metabolism (A.K.T.), Cukurova University, Faculty of Medicine, Balcali, 01330 Adana, Turkey.
Stephen O'RahillyPediatric Endocrinology (T.G., A.B., S.T., T.A., Z.A.), Marmara University Hospital, Altunizade, 34662 Istanbul, Turkey; University of Cambridge (F.R., F.M.G., G.T.), Department of Clinical Biochemistry, Addenbrooke's Hospital, Cambridge CB2 8RP, United Kingdom; University of Cambridge Metabolic Research Laboratories (N.R., K.P., S.O., R.K.S.), Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 8RP, United Kingdom; Forensic Medicine (L.D.K., H.C., A.S.), Cukurova University, Faculty of Medicine, Balcali, 01330 Adana, Turkey; and Pediatric Endocrinology and Metabolism (A.K.T.), Cukurova University, Faculty of Medicine, Balcali, 01330 Adana, Turkey.
Frank ReimannPediatric Endocrinology (T.G., A.B., S.T., T.A., Z.A.), Marmara University Hospital, Altunizade, 34662 Istanbul, Turkey; University of Cambridge (F.R., F.M.G., G.T.), Department of Clinical Biochemistry, Addenbrooke's Hospital, Cambridge CB2 8RP, United Kingdom; University of Cambridge Metabolic Research Laboratories (N.R., K.P., S.O., R.K.S.), Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 8RP, United Kingdom; Forensic Medicine (L.D.K., H.C., A.S.), Cukurova University, Faculty of Medicine, Balcali, 01330 Adana, Turkey; and Pediatric Endocrinology and Metabolism (A.K.T.), Cukurova University, Faculty of Medicine, Balcali, 01330 Adana, Turkey.
Robert K SemplePediatric Endocrinology (T.G., A.B., S.T., T.A., Z.A.), Marmara University Hospital, Altunizade, 34662 Istanbul, Turkey; University of Cambridge (F.R., F.M.G., G.T.), Department of Clinical Biochemistry, Addenbrooke's Hospital, Cambridge CB2 8RP, United Kingdom; University of Cambridge Metabolic Research Laboratories (N.R., K.P., S.O., R.K.S.), Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 8RP, United Kingdom; Forensic Medicine (L.D.K., H.C., A.S.), Cukurova University, Faculty of Medicine, Balcali, 01330 Adana, Turkey; and Pediatric Endocrinology and Metabolism (A.K.T.), Cukurova University, Faculty of Medicine, Balcali, 01330 Adana, Turkey.
A Kemal TopalogluPediatric Endocrinology (T.G., A.B., S.T., T.A., Z.A.), Marmara University Hospital, Altunizade, 34662 Istanbul, Turkey; University of Cambridge (F.R., F.M.G., G.T.), Department of Clinical Biochemistry, Addenbrooke's Hospital, Cambridge CB2 8RP, United Kingdom; University of Cambridge Metabolic Research Laboratories (N.R., K.P., S.O., R.K.S.), Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 8RP, United Kingdom; Forensic Medicine (L.D.K., H.C., A.S.), Cukurova University, Faculty of Medicine, Balcali, 01330 Adana, Turkey; and Pediatric Endocrinology and Metabolism (A.K.T.), Cukurova University, Faculty of Medicine, Balcali, 01330 Adana, Turkey.
Marmara University · TRUniversity of Cambridge · GBCukurova University · TRAddenbrooke's Hospital · GB
Funding
Medical Research Council G9824984Wellcome Trust 071187Wellcome Trust 080952Wellcome Trust 080952/Z/06/ZWellcome Trust 084210Wellcome Trust 084210/Z/07/Z
Abstract
contextThe neurokinin B (NKB) receptor, encoded by TACR3, is widely expressed within the central nervous system, including hypothalamic nuclei involved in regulating GnRH release. We have recently reported two mutations in transmembrane segments of the receptor and a missense mutation in NKB in patients with normosmic isolated hypogonadotropic hypogonadism (nIHH). PATIENTS AND
methodsWe sequenced the TACR3 gene in a family in which three siblings had nIHH. The novel mutant receptor thus identified was studied in a heterologous expression system using calcium flux as the functional readout.
resultsAll affected siblings were homozygous for the His148Leu mutation, in the first extracellular loop of the NKB receptor. The His148Leu mutant receptor exhibited profoundly impaired signaling in response to NKB (EC(50) = 3 +/- 0.1 nm and >5 microm for wild-type and His148Leu, respectively). The location of the mutation in an extracellular part of the receptor led us also to test whether senktide, a synthetic NKB analog, may retain ability to stimulate the mutant receptor. However, the signaling activity of the His148Leu receptor in response to senktide was also severely impaired (EC(50) = 1 +/- 1 nm for wild-type and no significant response of His148Leu to 10 microm).
conclusionsHomozygosity for the TACR3 His148Leu mutation leads to failure of sexual maturation in humans, whereas signaling by the mutant receptor in vitro in response to either NKB or senktide is severely impaired. These observations further strengthen the link between NKB, the NKB receptor, and regulation of human reproductive function.
Indexed as
Mutation, MissenseAdolescentAdultAmenorrheaBreastDNA Mutational AnalysisFemaleHistidineHomozygoteHormonesHumansHypogonadismLeucineMaleNeurokinin BPedigreeHistidineHormonesLeucineNeurokinin BPeptide FragmentsReceptors, Neurokinin-3senktideSubstance P
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