HPA axis dysregulation in mice overexpressing corticotropin releasing hormone

Biol Psychiatry. 2002 Jun 1;51(11):875-81. doi: 10.1016/s0006-3223(02)01334-3.


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.

MeSH terms

  • Adrenocorticotropic Hormone / blood
  • Animals
  • Corticotropin-Releasing Hormone / biosynthesis
  • Corticotropin-Releasing Hormone / blood
  • Corticotropin-Releasing Hormone / physiology*
  • Gene Expression Regulation
  • Genotype
  • Hypothalamo-Hypophyseal System / physiology*
  • Mice
  • Mice, Transgenic
  • Pituitary-Adrenal System / physiology*
  • Stress, Physiological / blood


  • Adrenocorticotropic Hormone
  • Corticotropin-Releasing Hormone