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Developmental Regulation of Glucocorticoid Receptor Processing in the Brain: Role of Specific E3 Ubiquitin Ligases
Author(s) -
DeFranco Donald B,
McCarran William,
MonaghanNichols Paula
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.231.3
Subject(s) - glucocorticoid receptor , downregulation and upregulation , glucocorticoid , receptor , nuclear receptor , hippocampal formation , hormone , biology , steroid hormone , transcription factor , ubiquitin ligase , endocrinology , medicine , microbiology and biotechnology , neuroscience , ubiquitin , gene , genetics
Glucocorticoid hormones exert a variety of effects on the brain and impact memory, anxiety, and CNS responses to stress. The action of these hormones is mediated primarily by soluble receptors, the corticosteroid or glucocorticoid receptors (GRs), which primarily act directly in the nucleus to regulate select networks of target genes. Many in vitro and in vivo model studies have revealed a relationship between expression levels of glucocorticoid receptors and cellular responsiveness to glucocorticoid hormone, particularly in the brain. Various intrinsic and extrinsic factors influence the expression of the glucocorticoid receptors and thereby impact cellular output to glucocorticoid hormone exposure. We had previously shown that the downregulation of GR expression that is characteristic of adult neurons, particular in the hippocampus, does not operate in fetal hippocampal neurons as GR levels are not affected by chronic hormone exposure. This lack of downregulation can be reversed in vitro by the overexpression of a specific E3 ligase for the receptor, carboxyl terminus of hsp70‐interacting protein (CHIP). The impact of CHIP expression in neurons on GR regulated transcription will be examined as well as the pattern of CHIP expression in developing brain, with a particular emphasis on GR responsive regions.