Regulation of the developing hypothalamic-pituitary-adrenal axis in corticotropin releasing hormone receptor 1-deficient mice

M. Schmidt, M. S. Oitzl, M. B. Müller, F. Ohl, W. Wurst, F. Holsboer, S. Levine, E. R. De Kloet

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

During postnatal development, mice undergo a so-called stress hyporesponsive period, which is characterized by low basal corticosterone levels and the inability of mild stressors to induce a corticosterone response. The stress hyporesponsiveness is in part regulated by maternal factors. Twenty-four hours of deprivation results in an activation of basal and stress-induced corticosterone and a down-regulation of corticotropin releasing hormone (CRH), mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) expression in the brain. It has been hypothesized that the CRH receptor 1 (CRHr1) may play an important regulatory role during development by mediating the effects of maternal deprivation. Using CRHr1-deficient mice we examined the role of this receptor on the maternal deprivation effects and in regulating the expression of hypothalamic-pituitary-adrenal axis-related genes. We could demonstrate that the CRHr1 is essential for the activation of the corticosterone response following maternal deprivation, most likely due to the lack of the receptor in the pituitary. Furthermore, we could show that the CRHr1 is regulating the expression of CRH and MRs. In contrast, effects of maternal deprivation during postnatal development on GRs are not mediated by this receptor.

Original languageEnglish
Pages (from-to)589-595
Number of pages7
JournalNeuroscience
Volume119
Issue number2
DOIs
StatePublished - 27 Jun 2003
Externally publishedYes

Keywords

  • Corticotropin releasing hormone
  • Maternal deprivation
  • Postnatal development
  • Stress system

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