title: HPA axis dysregulation in mice overexpressing corticotropin releasing hormone.
abstract: BACKGROUND
  Hypersecretion of corticotropin-releasing hormone (CRH) in the brain has been implicated in stress-related human pathologies. We developed a transgenic mouse line overexpressing CRH (CRH-OE) exclusively in neural tissues to assess the effect of long-term CRH overproduction on regulation of the hypothalamic-pituitary-adrenal (HPA) axis.
  
  
  METHODS
  Male transgenic CRH-OE(2122) mice on a C57BL/6J background were used. Littermate wildtype mice served as control animals. Basal plasma corticotropin and corticosterone concentrations were measured, and adrenal gland weight was determined. A dexamethasone suppression test measured the effects of long-term CRH hypersecretion on negative feedback control. Additionally, we measured plasma corticosterone concentrations in reaction to stress.
  
  
  RESULTS
  CRH-OE(2122) mice showed elevated basal plasma corticosterone concentrations, hypertrophy of the adrenal gland, and dexamethasone nonsuppression. Basal plasma ACTH concentrations of wildtype and CRH-OE(2122) mice did not differ significantly. In reaction to stress, CRH-OE(2122) mice showed a normal corticosterone response.
  
  
  CONCLUSIONS
  The HPA axis abnormalities observed in CRH-OE(2122) mice suggest that long-term hypersecretion of CRH in the brain can be a main cause of HPA axis dysregulation. The alterations in HPA axis regulation are reminiscent of changes reported in major depressive disorder. As such, these CRH -OE(2122) mice may model the neuroendocrine changes observed in major depressive disorder.
authors.affiliation: Department of Psychopharmacology, Utrecht University, Utrecht, The Netherlands.
authors.forename: Lucianne
authors.initials: L
authors.lastname: Groenink
authors.forename: Anneloes
authors.initials: A
authors.lastname: Dirks
authors.forename: P Monika
authors.initials: PM
authors.lastname: Verdouw
authors.forename: Marlies lutje
authors.initials: Ml
authors.lastname: Schipholt
authors.forename: Jan G
authors.initials: JG
authors.lastname: Veening
authors.forename: Jan
authors.initials: J
authors.lastname: van der Gugten
authors.forename: Berend
authors.initials: B
authors.lastname: Olivier
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis / Q000097:blood / Q000502:physiology*; D005786:Gene Expression Regulation; D005838:Genotype; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D010913:Pituitary-Adrenal System / Q000502:physiology*; D013312:Stress, Physiological / Q000097:blood
chemical_list: D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone