{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T07:08:11Z","timestamp":1779088091582,"version":"3.51.4"},"reference-count":10,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2017,8,4]],"date-time":"2017-08-04T00:00:00Z","timestamp":1501804800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,8,4]],"date-time":"2017-08-04T00:00:00Z","timestamp":1501804800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["EMBO Mol Med"],"published-print":{"date-parts":[[2017,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Hypogonadotropic hypogonadism is a syndrome found to be isolated (IHH) or associated with anosmia, corresponding to the Kallmann syndrome (KS). It comprises a defect in gonadotropin\u2010releasing hormone (GnRH) secretion and absent or delayed puberty. Genetic causes have been identified with a high genetic heterogeneity. Fibroblast growth factor receptor 1 (FGFR1), a tyrosine kinase receptor, was one of the first genes whose mutations were identified as causative in KS. FGFR1 is responsible for the formation of the GnRH neuron system. Studying patients has not only allowed the identification of new etiologies for this syndrome but also helped to unravel the signaling pathways involved in the development of GnRH neurons and in GnRH control and function. The FGF21\/FGFR1\/Klotho B (KLB) signaling\u00a0pathway mediates the response to starvation and other metabolic stresses. Preventing reproduction during nutritional deprivation is an adaptive process that is essential for the survival of species. In this work, Xu\n                    <jats:italic>et\u00a0al<\/jats:italic>\n                    (2017), using a candidate gene approach, provide a description of the essential role played by this pathway in GnRH biology and in the pathogenesis of IHH and KS. They establish a novel link between metabolism and reproduction in humans.\n                  <\/jats:p>","DOI":"10.15252\/emmm.201708180","type":"journal-article","created":{"date-parts":[[2017,8,4]],"date-time":"2017-08-04T20:10:15Z","timestamp":1501877415000},"page":"1334-1337","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["\u03b2\u2010Klotho sustains postnatal GnRH biology and spins the thread of puberty"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5379-8859","authenticated-orcid":false,"given":"Micheline","family":"Misrahi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,8,4]]},"reference":[{"key":"BFEMMM201708180_CR1","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/nrendo.2015.112","volume":"11","author":"U Boehm","year":"2015","unstructured":"Boehm U, Bouloux PM, Dattani MT, de Roux N, Dod\u00e9 C, Dunkel L, Dwyer AA, Giacobini P, Hardelin JP, Juul A et\u00a0al (2015) Expert consensus document: European Consensus Statement on congenital hypogonadotropic hypogonadism pathogenesis, diagnosis and treatment. Nat Rev Endocrinol 11: 547\u2013564","journal-title":"Nat Rev Endocrinol"},{"key":"BFEMMM201708180_CR2","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1056\/NEJMoa0911064","volume":"364","author":"LM Caronia","year":"2011","unstructured":"Caronia LM, Martin C, Welt CK, Sykiotis GP, Quinton R, Thambundit A, Avbelj M, Dhruvakumar S, Plummer L, Hughes VA et\u00a0al (2011) A genetic basis for functional hypothalamic amenorrhea. N Engl J Med 364: 215\u2013225","journal-title":"N Engl J Med"},{"key":"BFEMMM201708180_CR3","doi-asserted-by":"crossref","first-page":"4997","DOI":"10.1210\/en.2007-1634","volume":"149","author":"WC Chung","year":"2008","unstructured":"Chung WC, Moyle SS, Tsai PS (2008) Fibroblast growth factor 8 signaling through fibroblast growth factor receptor 1 is required for the emergence of gonadotropin\u2010releasing hormone neurons. Endocrinology 149: 4997\u20135003","journal-title":"Endocrinology"},{"key":"BFEMMM201708180_CR4","doi-asserted-by":"crossref","first-page":"2822","DOI":"10.1172\/JCI34538","volume":"118","author":"J Falardeau","year":"2008","unstructured":"Falardeau J, Chung WCJ, Beenken A, Raivio T, Plummer L, Sidis Y, Jacobson\u2010Dickman EE, Eliseenkova AV, Ma J, Dwyer A et\u00a0al (2008) Decreased FGF8 signaling causes deficiency of gonadotropin\u2010releasing hormone in humans and mice. J Clin Invest 118: 2822\u20132831","journal-title":"J Clin Invest"},{"key":"BFEMMM201708180_CR5","doi-asserted-by":"crossref","first-page":"1944","DOI":"10.1128\/MCB.06603-11","volume":"32","author":"R Goetz","year":"2012","unstructured":"Goetz R, Ohnishi M, Ding X, Kurosu H, Wang L, Akiyoshi J, Ma J, Gai W, Sidis Y, Pitteloud N et\u00a0al (2012) Klotho coreceptors inhibit signaling by paracrine fibroblast growth factor 8 subfamily ligands. Mol Cell Biol 32: 1944\u20131954","journal-title":"Mol Cell Biol"},{"key":"BFEMMM201708180_CR6","doi-asserted-by":"crossref","first-page":"7432","DOI":"10.1073\/pnas.0701600104","volume":"104","author":"Y Ogawa","year":"2007","unstructured":"Ogawa Y, Kurosu H, Yamamoto M, Nandi A, Rosenblatt KP, Goetz R, Eliseenkova AV, Mohammadi M, Kuro\u2010o M (2007) BetaKlotho is required for metabolic activity of fibroblast growth factor 21. Proc Natl Acad Sci USA 104: 7432\u20137437","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMMM201708180_CR7","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1038\/nm.3250","volume":"19","author":"BM Owen","year":"2013","unstructured":"Owen BM, Bookout AL, Ding X, Lin VY, Atkin SD, Gautron L, Kliewer SA, Mangelsdorf DJ (2013) FGF21 contributes to neuroendocrine control of female reproduction. Nat Med 19: 1153\u20131156","journal-title":"Nat Med"},{"key":"BFEMMM201708180_CR8","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.tem.2014.10.002","volume":"26","author":"BM Owen","year":"2015","unstructured":"Owen BM, Mangelsdorf DJ, Kliewer SA (2015) Tissue\u2010specific actions of the metabolic hormones FGF15\/19 and FGF21. Trends Endocrinol Metab 26: 22\u201329","journal-title":"Trends Endocrinol Metab"},{"key":"BFEMMM201708180_CR9","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1172\/JCI29884","volume":"117","author":"N Pitteloud","year":"2007","unstructured":"Pitteloud N, Quinton R, Pearce S, Raivio T, Acierno J, Dwyer A, Plummer L, Hughes V, Seminara S, Cheng YZ et\u00a0al (2007) Digenic mutations account for variable phenotypes in idiopathic hypogonadotropic hypogonadism. J Clin Invest 117: 457\u2013463","journal-title":"J Clin Invest"},{"key":"BFEMMM201708180_CR10","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.15252\/emmm.201607376","volume":"9","author":"C Xu","year":"2017","unstructured":"Xu C, Messina A, Somm E, Miraoui H, Kinnunen T, Acierno J, Niederl\u00e4nder NJ, Bouilly J, Dwyer AA, Sidis Y et\u00a0al (2017) KLB, encoding \u03b2\u2010Klotho, is mutated in patients with congenital hypogonadotropic hypogonadism. EMBO Mol Med 9: 1379\u20131397","journal-title":"EMBO Mol Med"}],"container-title":["EMBO Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.15252\/emmm.201708180.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.15252\/emmm.201708180","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.15252\/emmm.201708180\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.embopress.org\/doi\/pdf\/10.15252\/emmm.201708180","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.15252\/emmm.201708180.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T06:24:11Z","timestamp":1779085451000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.15252\/emmm.201708180"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,4]]},"references-count":10,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2017,10,1]]}},"alternative-id":["BFEMMM201708180"],"URL":"https:\/\/doi.org\/10.15252\/emmm.201708180","relation":{},"ISSN":["1757-4676","1757-4684"],"issn-type":[{"value":"1757-4676","type":"print"},{"value":"1757-4684","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,4]]},"assertion":[{"value":"4 August 2017","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The author declares that she has no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}