title: Hypothalamic gonadotropin-releasing hormone (GnRH) receptor neurons fire in synchrony with the female reproductive cycle.
abstract: Gonadotropin-releasing hormone (GnRH) controls mammalian reproduction via the hypothalamic-pituitary-gonadal (hpg) axis, acting on gonadotrope cells in the pituitary gland that express the GnRH receptor (GnRHR). Cells expressing the GnRHR have also been identified in the brain. However, the mechanism by which GnRH acts on these potential target cells remains poorly understood due to the difficulty of visualizing and identifying living GnRHR neurons in the central nervous system. We have developed a mouse strain in which GnRHR neurons express a fluorescent marker, enabling the reliable identification of these cells independent of the hormonal status of the animal. In this study, we analyze the GnRHR neurons of the periventricular hypothalamic nucleus in acute brain slices prepared from adult female mice. Strikingly, we find that the action potential firing pattern of these neurons alternates in synchrony with the estrous cycle, with pronounced burst firing during the preovulatory period. We demonstrate that GnRH stimulation is sufficient to trigger the conversion from tonic to burst firing in GnRHR neurons. Furthermore, we show that this switch in the firing pattern is reversed by a potent GnRHR antagonist. These data suggest that endogenous GnRH acts on GnRHR neurons and triggers burst firing in these cells during late proestrus and estrus. Our data have important clinical implications in that they indicate a novel mode of action for GnRHR agonists and antagonists in neurons of the central nervous system that are not part of the classical hpg axis.
authors.affiliation: Department of Physiology and Center for Integrative Physiology and Molecular Medicine, University of Saarland School of Medicine, Homburg, Germany;
authors.forename: Christian
authors.initials: C
authors.lastname: Schauer
authors.affiliation: Department of Physiology and Center for Integrative Physiology and Molecular Medicine, University of Saarland School of Medicine, Homburg, Germany;
authors.forename: Tong
authors.initials: T
authors.lastname: Tong
authors.affiliation: Department of Physiology and Center for Integrative Physiology and Molecular Medicine, University of Saarland School of Medicine, Homburg, Germany;
authors.forename: Hugues
authors.initials: H
authors.lastname: Petitjean
authors.affiliation: Department of Physiology and Center for Integrative Physiology and Molecular Medicine, University of Saarland School of Medicine, Homburg, Germany;
authors.forename: Thomas
authors.initials: T
authors.lastname: Blum
authors.affiliation: Department of Physiology and Center for Integrative Physiology and Molecular Medicine, University of Saarland School of Medicine, Homburg, Germany;
authors.forename: Sophie
authors.initials: S
authors.lastname: Peron
authors.affiliation: Department of Pharmacology and Toxicology, University of Saarland School of Medicine, Homburg, Germany; and.
authors.forename: Oliver
authors.initials: O
authors.lastname: Mai
authors.affiliation: Department of Anatomy, University of Saarland School of Medicine, Homburg, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Schmitz
authors.affiliation: Department of Pharmacology and Toxicology, University of Saarland School of Medicine, Homburg, Germany; and.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Boehm
authors.affiliation: Department of Physiology and Center for Integrative Physiology and Molecular Medicine, University of Saarland School of Medicine, Homburg, Germany; trese.leinders@uks.eu.
authors.forename: Trese
authors.initials: T
authors.lastname: Leinders-Zufall
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002196:Capillaries / Q000648:ultrastructure; D030762:Estrous Cycle / Q000187:drug effects / Q000502:physiology*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006727:Hormone Antagonists / Q000494:pharmacology; D007031:Hypothalamus / Q000098:blood supply / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D007150:Immunohistochemistry; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D009474:Neurons / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D011966:Receptors, LHRH / Q000037:antagonists & inhibitors / Q000378:metabolism; D046509:Tissue Culture Techniques
chemical_list: D006727:Hormone Antagonists; D011966:Receptors, LHRH; D049452:Green Fluorescent Proteins; D007987:Gonadotropin-Releasing Hormone; C062876:cetrorelix
keywords: cetrorelix; gonadotropin-releasing hormone; hypothalamus