Novel role for anti-Müllerian hormone in the regulation of GnRH neuron excitability and hormone secretion

• DOI: 10.1038/ncomms10055
• Publication Date: 2016-01-12T11:41:28Z
• Authors: Irene Cimino; Filippo Casoni; Xinhuai Liu; Andrea Messina; Jyoti Parkash; Soazik P. Jamin; Sophie Catteau-Jo...; Francis Collier; Marc Baroncini; Didier Dewailly; Pascal Pigny; Mel Prescott; Rebecca Campbell; Allan E. Herbison; Vincent Prevot; Paolo Giacobini
• Keywords: Anti-Mullerian Hormone; 0301 basic medicine; Receptors, Peptide; [SDV]Life Sciences [q-bio]; Science; Hypothalamus; Enzyme-Linked Immunosorbent Assay; In Vitro Techniques; Animals; Anti-Mullerian Hormone; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Follicle Stimulating Hormone; Gene Knock-In Techniques; Gonadotropin-Releasing Hormone; Humans; Hypothalamus; Immunohistochemistry; In Vitro Techniques; Luteinizing Hormone; Mice; Neurons; Polycystic Ovary Syndrome; Rats, Sprague-Dawley; Receptors, Peptide; Receptors, Transforming Growth Factor beta; Reverse Transcriptase Polymerase Chain Reaction; Article; Gonadotropin-Releasing Hormone; Rats, Sprague-Dawley; Mice; 03 medical and health sciences; Animals; Humans; Gene Knock-In Techniques; Neurons; Q; Luteinizing Hormone; Flow Cytometry; Immunohistochemistry; Disease Models, Animal; Female; Follicle Stimulating Hormone; Receptors, Transforming Growth Factor beta; Polycystic Ovary Syndrome

AbstractAnti-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. Combiningin vivoandin vitroexperiments, 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.