title: Loss of NSCL-2 in gonadotropin releasing hormone neurons leads to reduction of pro-opiomelanocortin neurons in specific hypothalamic nuclei and causes visceral obesity.
abstract: Regulation of sexual reproduction and energy homeostasis are closely interconnected, but only few efforts were made to explore the impact of gonadotropic neurons on metabolic processes. We have used Nscl-2 mutant mice suffering from adult onset of obesity and hypogonadotropic hypogonadism to study effects of gonadotropin releasing hormone (GnRH) neurons on neuronal circuits controlling energy balance. Inactivation of Nscl-2 in GnRH neurons but not in pro-opiomelanocortin (POMC) neurons reduced POMC neurons and increased visceral fat mass, suggesting a critical role of GnRH cells in the regulation of POMC neurons. In contrast, absence of POMC processing in the majority of Nscl-2-deficient POMC neurons had no effect on energy homeostasis. Finally, we investigated the cellular basis of the reduction of GnRH neurons in NSCL-2 mutants using a lineage tracing approach. We found that loss of Nscl-2 results in aberrant migration of GnRH neurons in Nscl-2 mutant mice causing a lineage switch of ectopically located GnRH neurons.
authors.affiliation: Max Planck Institute for Heart and Lung Research, D-61231 Bad Nauheim, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schmid
authors.forename: Stefan
authors.initials: S
authors.lastname: Günther
authors.forename: Luca
authors.initials: L
authors.lastname: Mendler
authors.forename: Thomas
authors.initials: T
authors.lastname: Braun
mesh_terms: D000273:Adipose Tissue / Q000254:growth & development / Q000502:physiology; D000324:Adrenocorticotropic Hormone / Q000378:metabolism / Q000502:physiology; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000502:physiology*; D015153:Blotting, Western; D002455:Cell Division / Q000502:physiology; D004958:Estradiol / Q000097:blood; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics* / Q000502:physiology*; D006706:Homeostasis / Q000235:genetics / Q000502:physiology; D007031:Hypothalamus / Q000502:physiology*; D007034:Hypothalamus, Posterior / Q000502:physiology; D007246:Infertility / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D009765:Obesity / Q000235:genetics*; D011301:Preoptic Area / Q000502:physiology; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D012098:Reproduction / Q000235:genetics / Q000502:physiology
chemical_list: D000324:Adrenocorticotropic Hormone; D051792:Basic Helix-Loop-Helix Proteins; D004958:Estradiol; D007987:Gonadotropin-Releasing Hormone; D011333:Pro-Opiomelanocortin; C484104:Nhlh2 protein, mouse