PT  - JOURNAL ARTICLE
AU  - Philip A. Iredale
AU  - Ronald S. Duman
TI  - Glucocorticoid Regulation of Corticotropin-Releasing Factor<sub>1</sub> Receptor Expression in Pituitary-Derived AtT-20 Cells
AID  - 10.1124/mol.51.5.794
DP  - 1997 May 01
TA  - Molecular Pharmacology
PG  - 794--799
VI  - 51
IP  - 5
4099  - http://molpharm.aspetjournals.org/content/51/5/794.short
4100  - http://molpharm.aspetjournals.org/content/51/5/794.full
SO  - Mol Pharmacol1997 May 01; 51
AB  - 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 results demonstrate that glucocorticoid incubation significantly decreases CRF-R1 mRNA stability by approximately 50%. The down-regulation of CRF-R1 mRNA was dependent onde 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.