Glucocorticoid regulation of corticotropin-releasing factor1 receptor expression in pituitary-derived AtT-20 cells.
Mol Pharmacol
; 51(5): 794-9, 1997 May.
Article
en En
| MEDLINE
| ID: mdl-9145917
Corticotropin-releasing factor (CRF) receptors represent one of the primary sites for negative feedback of the pituitary by adrenocortical glucocorticoid hormones; however, the molecular mechanisms involved have yet to be elucidated. The present study examines the mechanisms by which glucocorticoids regulate CRF-R1 expression in the pituitary cell line, AtT-20. Treatment of these cells with dexamethasone resulted in a concentration- and time-dependent inhibition of CRF-R1 mRNA that was significant by 1 hr and maximal after 4 hr. Levels of CRF-R1 mRNA then returned to control levels after 24 hr. Similar changes were observed when the cells were treated with corticosterone. Pro-opiomelanocortin mRNA was also decreased after dexamethasone pretreatment; however, the time course was much slower with a significant effect only detected after 6 hr. Further analysis of the mechanisms that mediate glucocorticoid regulation of CRF-R1 mRNA was conducted These studies demonstrated that glucocorticoid incubation significantly decreases the rate of CRF-R1 gene transcription, as determined by nuclear run-on analysis. In addition, the result demonstrate that glucocorticoid incubation significantly decreases CRF-R1 mRNA stability by approximately 50%. The down-regulation of CRF-R1 mRNA was dependent on de novo protein synthesis, as it was blocked by pretreatment with cycloheximide. This represents a novel mechanism for glucocorticoid negative feedback regulation of CRF-R1 expression.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Hipófisis
/
Dexametasona
/
Regulación de la Expresión Génica
/
Receptores de Hormona Liberadora de Corticotropina
Idioma:
En
Revista:
Mol Pharmacol
Año:
1997
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos