Involvement of regulatory elements on corticotropin-releasing factor gene promoter in hypothalamic 4B cells

Corticotropin-releasing factor (CRF) plays a central role in controlling the hypothalamic-pituitary-adrenal (HPA) axis during stressful periods. CRF is synthesized and secreted in the hypothalamic paraventricular nucleus (PVN) in response to stress, and stimulates ACTH in the pituitary corticotrophs...

Full description

Saved in:
Bibliographic Details
Published in:Journal of endocrinological investigation 2008-12, Vol.31 (12), p.1079
Main Authors: Kageyama, K, Hanada, K, Takayasu, S, Iwasaki, Y, Sakihara, S, Nigawara, T, Suda, T
Format: Article
Language:English
Subjects:
Anthracenes - pharmacology
Cell Line
Chromones - pharmacology
Colforsin - pharmacology
Corticotropin-Releasing Hormone - genetics
Corticotropin-Releasing Hormone - metabolism
Dexamethasone - pharmacology
Flavonoids - pharmacology
Genes, Reporter - drug effects
Humans
Hypothalamus - drug effects
Hypothalamus - metabolism
Imidazoles - pharmacology
Isoquinolines - pharmacology
Morpholines - pharmacology
Promoter Regions, Genetic - drug effects
Promoter Regions, Genetic - physiology
Protein Kinase Inhibitors - pharmacology
Pyridines - pharmacology
Regulatory Elements, Transcriptional - drug effects
Regulatory Elements, Transcriptional - physiology
Sequence Deletion
Sulfonamides - pharmacology
Transfection
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Corticotropin-releasing factor (CRF) plays a central role in controlling the hypothalamic-pituitary-adrenal (HPA) axis during stressful periods. CRF is synthesized and secreted in the hypothalamic paraventricular nucleus (PVN) in response to stress, and stimulates ACTH in the pituitary corticotrophs. ACTH stimulates the release of glucocorticoids from the adrenal glands, and glucocorticoids sequentially inhibit hypothalamic PVN production of CRF and pituitary production of ACTH. The effects of glucocorticoids on CRF gene regulation, however, are possibly tissue-specific since glucocorticoids stimulate CRF gene expression in the placenta and the bed nucleus of the stria terminalis, while they inhibit it in the hypothalamus. In a hypothalamic cell line, 4B, we found that forskolin-stimulated CRF gene transcription was mediated by a functional cAMP-response element (CRE), which included -220 to -233 bp on the CRF 5'-promoter region. Protein kinase A, protein kinase C, and p38 mitogen-activated protein kinase pathways contributed to forskolin-induced transcriptional activity of CRF in hypothalamic 4B cells. Glucocorticoid-dependent repression of cAMP-stimulated transcriptional activity of CRF was localized to promoter sequences between -278 and -233 bp, which included a glucocorticoid regulatory element and a serum response element. Taken together, these findings indicate that the regulatory elements, including CRE, negative glucocorticoid regulatory element, and a serum response element on the promoter, contribute to the regulation of CRF gene transcription in hypothalamic 4B cells.
ISSN:1720-8386
DOI:10.1007/BF03345656