ISSN:
1365-2826
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Corticotropin-releasing factor (CRF) is a major secretagogue of adrenocorticotopic hormone from the anterior pituitary and a key activator of the hypothalamic-pituitary-adrenal axis. We previously reported that CRF down-regulates expression of the CRF type-1 receptor (CRF-R1) mRNA in cultured rat anterior pituitary cells. The present study was conducted to clarify the signal transduction systems involved in CRF-induced down-regulation of CRF-R1 gene expression in the anterior pituitary. Northern blot analysis revealed that, under serum-free conditions, 10 nM CRF decreased CRF-R1 mRNA levels in cultured rat anterior pituitary cells as we reported previously. Treatment with 5 mM 8-Br-cAMP reduced CRF-R1 mRNA levels within 2 h. The mRNA level fell to 37±3% of the basal level at 2 h and remained low for 16 h after treatment. This CRF-induced reduction of CRF-R1 mRNA expression was inhibited completely by pretreatment with protein kinase A (PKA) inhibitor (1 µM H-89). Further examination revealed that after pretreatment with 10 µM of antisense oligodeoxynucleotide for cyclic AMP-response element binding protein (CREB), the CRF-induced inhibition of CRF-R1 mRNA was partially decreased to 79±4% of the control level 2 h after administration of CRF. These findings indicate that CRF may down-regulate CRF-R1 mRNA expression via a cAMP-PKA-mediated mechanism in rat anterior pituitary cells, and that CREB may mediate at least a portion of this inhibitory effect.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1365-2826.2002.00816.x
