title: Overexpression of corticotropin-releasing hormone in transgenic mice and chronic stress-like autonomic and physiological alterations.
abstract: To gain a greater insight into the relationship between hyperactivity of the corticotropin-releasing hormone (CRH) system and autonomic and physiological changes associated with chronic stress, we developed a transgenic mouse model of central CRH overproduction. The extent of central and peripheral CRH overexpression, and the amount of bioactive CRH in the hypothalamus were determined in two lines of CRH-overexpressing (CRH-OE) mice. Furthermore, 24 h patterns of body temperature, heart rate, and activity were assessed using radiotelemetry, as well as cumulative water and food consumption and body weight gain over a 7-day period. CRH-OE mice showed increased amounts of CRH peptide and mRNA only in the central nervous system. Despite the presence of the same CRH transgene in their genome, only in one of the two established lines of CRH-OE mice (line 2122, but not 2123) was overexpression of CRH associated with increased levels of bioactive CRH in the hypothalamus, increased body temperature and heart rate (predominantly during the light (inactive) phase of the diurnal cycle), decreased heart rate variability during the dark (active) phase, and increased food and water consumption, when compared with littermate wildtype mice. Because line 2122 of the CRH transgenic mice showed chronic stress-like neuroendocrine and autonomic changes, these mice appear to represent a valid animal model for chronic stress and might be valuable in the research on the consequences of CRH excess in situations of chronic stress.
authors.affiliation: Department of Psychopharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands. A.Dirks@pharm.uu.nl
authors.forename: Anneloes
authors.initials: A
authors.lastname: Dirks
authors.forename: Lucianne
authors.initials: L
authors.lastname: Groenink
authors.forename: J Adriaan
authors.initials: JA
authors.lastname: Bouwknecht
authors.forename: Theo H
authors.initials: TH
authors.lastname: Hijzen
authors.forename: Jan
authors.initials: J
authors.lastname: Van Der Gugten
authors.forename: Eric
authors.initials: E
authors.lastname: Ronken
authors.forename: J Sjef
authors.initials: JS
authors.lastname: Verbeek
authors.forename: Jan G
authors.initials: JG
authors.lastname: Veening
authors.forename: Pieter J W C
authors.initials: PJ
authors.lastname: Dederen
authors.forename: Aniko
authors.initials: A
authors.lastname: Korosi
authors.forename: Louise F
authors.initials: LF
authors.lastname: Schoolderman
authors.forename: Eric W
authors.initials: EW
authors.lastname: Roubos
authors.forename: Berend
authors.initials: B
authors.lastname: Olivier
mesh_terms: D000818:Animals; D001341:Autonomic Nervous System / Q000502:physiology*; D001831:Body Temperature / Q000502:physiology; D002490:Central Nervous System / Q000737:chemistry / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000032:analysis / Q000378:metabolism*; D006339:Heart Rate / Q000502:physiology; D007031:Hypothalamus / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic / Q000276:immunology / Q000502:physiology; D013312:Stress, Physiological; D015854:Up-Regulation / Q000502:physiology
chemical_list: D003346:Corticotropin-Releasing Hormone