title: Novel role for anti-Müllerian hormone in the regulation of GnRH neuron excitability and hormone secretion.
abstract: Anti-Müllerian hormone (AMH) plays crucial roles in sexual differentiation and gonadal functions. However, the possible extragonadal effects of AMH on the hypothalamic-pituitary-gonadal axis remain unexplored. Here we demonstrate that a significant subset of GnRH neurons both in mice and humans express the AMH receptor, and that AMH potently activates the GnRH neuron firing in mice. Combining in vivo and in vitro experiments, we show that AMH increases GnRH-dependent LH pulsatility and secretion, supporting a central action of AMH on GnRH neurons. Increased LH pulsatility is an important pathophysiological feature in many cases of polycystic ovary syndrome (PCOS), the most common cause of female infertility, in which circulating AMH levels are also often elevated. However, the origin of this dysregulation remains unknown. Our findings raise the intriguing hypothesis that AMH-dependent regulation of GnRH release could be involved in the pathophysiology of fertility and could hold therapeutic potential for treating PCOS.
authors.affiliation: Inserm, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Jean-Pierre Aubert Research Centre, U1172, Lille 59045, France.|University of Lille, FHU 1,000 Days for Health, School of Medicine and SFR DN2M, Lille 59045, France.
authors.forename: Irene
authors.initials: I
authors.lastname: Cimino
authors.affiliation: Inserm, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Jean-Pierre Aubert Research Centre, U1172, Lille 59045, France.|University of Lille, FHU 1,000 Days for Health, School of Medicine and SFR DN2M, Lille 59045, France.
authors.forename: Filippo
authors.initials: F
authors.lastname: Casoni
authors.affiliation: Centre for Neuroendocrinology and Department of Physiology, University of Otago School of Medical Sciences, Dunedin 9054, New Zealand.
authors.forename: Xinhuai
authors.initials: X
authors.lastname: Liu
authors.affiliation: Inserm, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Jean-Pierre Aubert Research Centre, U1172, Lille 59045, France.|University of Lille, FHU 1,000 Days for Health, School of Medicine and SFR DN2M, Lille 59045, France.
authors.forename: Andrea
authors.initials: A
authors.lastname: Messina
authors.affiliation: Inserm, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Jean-Pierre Aubert Research Centre, U1172, Lille 59045, France.|University of Lille, FHU 1,000 Days for Health, School of Medicine and SFR DN2M, Lille 59045, France.
authors.forename: Jyoti
authors.initials: J
authors.lastname: Parkash
authors.affiliation: Inserm U1085-IRSET, Université de Rennes 1, Rennes 35042, France.
authors.forename: Soazik P
authors.initials: SP
authors.lastname: Jamin
authors.affiliation: Inserm, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Jean-Pierre Aubert Research Centre, U1172, Lille 59045, France.|University of Lille, FHU 1,000 Days for Health, School of Medicine and SFR DN2M, Lille 59045, France.|Service de Gynécologie Endocrinienne et Médecine de la Reproduction, Hôpital Jeanne de Flandre, CHU de Lille, Lille 59037, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Catteau-Jonard
authors.affiliation: University of Lille, FHU 1,000 Days for Health, School of Medicine and SFR DN2M, Lille 59045, France.|Service de Gynécologie Endocrinienne et Médecine de la Reproduction, Hôpital Jeanne de Flandre, CHU de Lille, Lille 59037, France.
authors.forename: Francis
authors.initials: F
authors.lastname: Collier
authors.affiliation: Inserm, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Jean-Pierre Aubert Research Centre, U1172, Lille 59045, France.|University of Lille, FHU 1,000 Days for Health, School of Medicine and SFR DN2M, Lille 59045, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Baroncini
authors.affiliation: Inserm, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Jean-Pierre Aubert Research Centre, U1172, Lille 59045, France.|University of Lille, FHU 1,000 Days for Health, School of Medicine and SFR DN2M, Lille 59045, France.|Service de Gynécologie Endocrinienne et Médecine de la Reproduction, Hôpital Jeanne de Flandre, CHU de Lille, Lille 59037, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Dewailly
authors.affiliation: University of Lille, FHU 1,000 Days for Health, School of Medicine and SFR DN2M, Lille 59045, France.|Laboratoire de Biochimie &Hormonologie, Centre de Biologie Pathologie, Centre Hospitalier Régional Universitaire, CHU de Lille, Lille 59037, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Pigny
authors.affiliation: Centre for Neuroendocrinology and Department of Physiology, University of Otago School of Medical Sciences, Dunedin 9054, New Zealand.
authors.forename: Mel
authors.initials: M
authors.lastname: Prescott
authors.affiliation: Centre for Neuroendocrinology and Department of Physiology, University of Otago School of Medical Sciences, Dunedin 9054, New Zealand.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Campbell
authors.affiliation: Centre for Neuroendocrinology and Department of Physiology, University of Otago School of Medical Sciences, Dunedin 9054, New Zealand.
authors.forename: Allan E
authors.initials: AE
authors.lastname: Herbison
authors.affiliation: Inserm, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Jean-Pierre Aubert Research Centre, U1172, Lille 59045, France.|University of Lille, FHU 1,000 Days for Health, School of Medicine and SFR DN2M, Lille 59045, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Prevot
authors.affiliation: Inserm, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Jean-Pierre Aubert Research Centre, U1172, Lille 59045, France.|University of Lille, FHU 1,000 Days for Health, School of Medicine and SFR DN2M, Lille 59045, France.
authors.forename: Paolo
authors.initials: P
authors.lastname: Giacobini
mesh_terms: D000818:Animals; D054304:Anti-Mullerian Hormone / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D055879:Gene Knock-In Techniques; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D006801:Humans; D007031:Hypothalamus / Q000166:cytology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007986:Luteinizing Hormone / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D011085:Polycystic Ovary Syndrome / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D018000:Receptors, Peptide / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018000:Receptors, Peptide; D018125:Receptors, Transforming Growth Factor beta; C084621:anti-Mullerian hormone receptor; D007987:Gonadotropin-Releasing Hormone; D054304:Anti-Mullerian Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone