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Lookup NU author(s): Dr Richard Quinton
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© 2019, Malone et al.Congenital hypogonadotropic hypogonadism (CHH) is a condition characterized by absent puberty and infertility due to gonadotropin releasing hormone (GnRH) deficiency, which is often associated with anosmia (Kallmann syndrome, KS). We identified loss-of-function heterozygous mutations in anti-Müllerian hormone (AMH) and its receptor, AMHR2, in 3% of CHH probands using whole-exome sequencing. We showed that during embryonic development, AMH is expressed in migratory GnRH neurons in both mouse and human fetuses and unconvered a novel function of AMH as a pro-motility factor for GnRH neurons. Pathohistological analysis of Amhr2-deficient mice showed abnormal development of the peripheral olfactory system and defective embryonic migration of the neuroendocrine GnRH cells to the basal forebrain, which results in reduced fertility in adults. Our findings highlight a novel role for AMH in the development and function of GnRH neurons and indicate that AMH signaling insufficiency contributes to the pathogenesis of CHH in humans.
Author(s): Malone SA, Papadakis GE, Messina A, Mimouni NEH, Trova S, Imbernon M, Allet C, Cimino I, Acierno J, Cassatella D, Xu C, Quinton R, Szinnai G, Pigny P, Alonso-Cotchico L, Masgrau L, Marechal J-D, Prevot V, Pitteloud N, Giacobini P
Publication type: Article
Publication status: Published
Journal: eLife
Year: 2019
Volume: 8
Online publication date: 10/07/2019
Acceptance date: 28/06/2019
Date deposited: 05/08/2019
ISSN (electronic): 2050-084X
Publisher: eLife Sciences Publications
URL: https://doi.org/10.7554/eLife.47198
DOI: 10.7554/eLife.47198
PubMed id: 31291191
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