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dc.contributor.authorYoung, Jacques
dc.contributor.authorGeorge, Jyothis
dc.contributor.authorTello, Javier
dc.contributor.authorFrancou, Bruno
dc.contributor.authorBouligand, Jerome
dc.contributor.authorGuiochon-Mantel, Anne
dc.contributor.authorBrailly-Tabard, Sylvie
dc.contributor.authorAnderson, Richard
dc.contributor.authorMillar, Robert
dc.date.accessioned2014-12-22T12:31:01Z
dc.date.available2014-12-22T12:31:01Z
dc.date.issued2013-03
dc.identifier.citationYoung , J , George , J , Tello , J , Francou , B , Bouligand , J , Guiochon-Mantel , A , Brailly-Tabard , S , Anderson , R & Millar , R 2013 , ' Kisspeptin restores pulsatile LH secretion in patients with neurokinin B signaling deficiencies : physiological, pathophysiological and therapeutic implications ' , Neuroendocrinology , vol. 97 , no. 2 , pp. 193-202 . https://doi.org/10.1159/000336376en
dc.identifier.issn0028-3835
dc.identifier.otherPURE: 50364610
dc.identifier.otherPURE UUID: 5683d950-6f9c-4904-82f1-49d42e731b73
dc.identifier.otherWOS: 000316737000008
dc.identifier.otherScopus: 84876289515
dc.identifier.otherORCID: /0000-0001-6637-2155/work/64034493
dc.identifier.urihttp://hdl.handle.net/10023/5948
dc.description.abstractPulsatile gonadotropin-releasing hormone (GnRH) is crucial to normal reproductive function and abnormalities in pulse frequency give rise to reproductive dysfunction. Kisspeptin and neurokinin B (NKB), neuropeptides secreted by the same neuronal population in the ventral hypothalamus, have emerged recently as critical central regulators of GnRH and thus gonadotropin secretion. Patients with mutations resulting in loss of signaling by either of these neuroendocrine peptides fail to advance through puberty but the mechanisms mediating this remain unresolved. We report here that continuous kisspeptin infusion restores gonadotropin pulsatility in patients with loss-of-function mutations in NKB (TAC3) or its receptor (TAC3R), indicating that kisspeptin on its own is sufficient to stimulate pulsatile GnRH secretion. Moreover, our findings suggest that NKB action is proximal to kisspeptin in the reproductive neuroendocrine cascade regulating GnRH secretion, and may act as an autocrine modulator of kisspeptin secretion. The ability of continuous kisspeptin infusion to induce pulsatile gonadotropin secretion further indicates that GnRH neurons are able to set up pulsatile secretion in the absence of pulsatile exogenous kisspeptin.
dc.language.isoeng
dc.relation.ispartofNeuroendocrinologyen
dc.rights© 2012 S. Karger AG, Basel This is an Open Access article licensed under the terms of the Creative Commons Attribution 3.0 Unported license (CC BY 3.0) (http://www.karger.com/Services/OpenAccessLicenseWt), applicable to the online version of the article only.en
dc.subjectDeficient NKB signalingen
dc.subjectGnRH pulse generationen
dc.subjectKisspeptinen
dc.subjectKisspeptin-10 infusionen
dc.subjectNeurokinin B signaling deficiencyen
dc.subjectPulsatile LH secretionen
dc.subjectHypogonadotropic hypogonadism
en
dc.subjectRC Internal medicineen
dc.subject.lccRCen
dc.titleKisspeptin restores pulsatile LH secretion in patients with neurokinin B signaling deficiencies : physiological, pathophysiological and therapeutic implicationsen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Medicineen
dc.contributor.institutionUniversity of St Andrews.Biomedical Sciences Research Complexen
dc.identifier.doihttps://doi.org/10.1159/000336376
dc.description.statusPeer revieweden


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