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

M Schmidt*, MS Oitzl, MB Muller, F Ohl, W Wurst, F Holsboer, S Levine, ER De Kloet, Frauke Ohl

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    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. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved.

    Original languageEnglish
    Pages (from-to)589-595
    Number of pages7
    JournalNeuroscience
    Volume119
    Issue number2
    DOIs
    Publication statusPublished - 2003

    Keywords

    • stress system
    • corticotropin releasing hormone
    • maternal deprivation
    • postnatal development
    • MESSENGER-RIBONUCLEIC-ACID
    • IMPAIRED STRESS-RESPONSE
    • MATERNAL-DEPRIVATION
    • PARAVENTRICULAR NUCLEUS
    • TRANSGENIC MICE
    • INFANT RAT
    • FACTOR CRF
    • REDUCED ANXIETY
    • EXPRESSION
    • SYSTEM

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