Involvement of regulatory elements on corticotropin-releasing factor gene promoter in hypothalamic 4B cells.
J Endocrinol Invest
; 31(12): 1079-85, 2008 Dec.
Article
em En
| MEDLINE
| ID: mdl-19246974
ABSTRACT
INTRODUCTION:
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. METHODS ANDRESULTS:
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.CONCLUSION:
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Hormônio Liberador da Corticotropina
/
Elementos Reguladores de Transcrição
/
Hipotálamo
Limite:
Humans
Idioma:
En
Revista:
J Endocrinol Invest
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Japão
País de publicação:
IT
/
ITALIA
/
ITALY
/
ITÁLIA