Characterization of the human corticotropin-releasing factor2(a) receptor promoter: regulation by glucocorticoids and the cyclic adenosine 5'-monophosphate pathway

Endocrinology
Steven A NandaNed H Kalin

Abstract

Corticotropin-releasing factor (CRF) is a neurotransmitter and hormone believed to integrate responses to stress. Evidence suggests central CRF systems are overactive in some individuals suffering from depression and anxiety disorders. CRF receptor antagonism blocks stress-induced endocrine, autonomic, and behavioral effects in animal models, and studies have implicated the CRF2 receptor in anxiety-related behaviors. Greater understanding of the regulation of CRF2 expression may facilitate understanding mechanisms underlying anxiety. The present studies are the first to characterize the transcriptional regulation of the human CRF2(a), the predominant CRF2 isoform in brain. Four kilobase pairs of sequence immediately upstream of the first exon of CRF2(a) represented our full-length promoter region. Sequentially smaller fragments of the CRF2(a) promoter region were generated by PCR and cloned upstream of a luciferase reporter gene. Expression was monitored from these constructs within Chinese hamster ovary-K1 cells and within rat aortic A7R5 cells that express CRF2. Glucocorticoid treatment decreased expression and elevating intracellular cAMP increased expression from the human CRF2(a) promoter. The regions of the CRF2(a) promot...Continue Reading

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