DIFFERENTIAL REGULATION OF CORTICOTROPIN-RELEASING FACTOR(1) RECEPTOREXPRESSION BY STRESS AND AGONIST TREATMENTS IN BRAIN AND CULTURED-CELLS

Corticotropin-releasing factor (CRF) is known to play a major role in coordinating neuroendocrine and behavioral responses to stress. We dem onstrate that expression of the CRF(1) receptor (CRF-R1) is regulated by stress in the brain and by agonist treatments in cultured cells. Ex pression of CRF-R1 mRNA was decreased in the frontal cortex but increa sed in the hippocampus by chronic unpredictable stress. Chronic cortic osterone administration did not influence levels of CRF-R1 mRNA in eit her region, suggesting that regulation of CRF-R1 expression is mediate d by CRF itself or by another stress-related factor. Differential regu lation of CRF-R1 mRNA by agonist treatment was also observed in two cu ltured cell lines. In CATH.a cells, a neuron-derived cell line, incuba tion with CRF decreased levels of CRF-R1 mRNA, whereas in AtT-20 cells , a pituitary-derived cell line, agonist (CRF) treatment increased lev els of CRF-R1 mRNA. Further studies demonstrated that the observed cha nges in both cell lines could be accounted for by regulation of CRF-R1 gene transcription and not by altered mRNA stability. Furthermore, ag onist-induced down-regulation of CRF-R1 transcription rate in CATH.a c ells was found to be dependent on de novo protein synthesis, suggestin g the involvement of an inducible repressor. The results show that dif ferent cell types show differential transcriptional regulation of the CRF-R1, which could explain the region-specific regulation of receptor expression in the brain.