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    Effects of a novel corticotropin-releasing-hormone receptor type I antagonist on human adrenal function.
        
        Mol. Psychiatry 5, 137-141 (2000)
    
    
    
	    Corticotropin-releasing hormone (CRH) is the principal regulator of the hypothalamic-pituitary-adrenal (HPA) axis and an activator of the sympathoadrenal (SA) and systemic sympathetic (SS) systems. Mental disorders, including major depression and, more recently, Alzheimer's disease have been associated with dysregulation of the HPA axis and the SA/SS systems. Treatment of rats or monkeys with the novel CRH receptor type 1 (CRH-R1) antagonist antalarmin inhibits the HPA and/or the SA/SS axes. This is the first study to examine the potential direct effect of antalarmin on human adrenal function. Adrenocortical and adrenomedullary cells were characterized by double-immunohistochemistry with anti-17 alpha hydroxylase (cortical cells) and anti-chromogranin A (chromaffin cells). Expression of CRH, ACTH, CRH type I and type II receptor mRNA were analyzed by reverse-transcription (RT) PCR. Human adrenal cortical and/or chromaffin cells in co-culture were incubated with CRH, antalarmin, and both CRH and antalarmin in vitro. Exposure of these cells to corticotropin or vehicle medium served as positive and negative controls, respectively. Cortical and chromaffin tissues were interwoven in the human adrenals, and both in situ and in the co-culture system the endocrine cell types were in close cellular contact. ACTH, CRH, and CRH-R1 and CRH-R2 mRNAs were expressed in the human adrenal as determined by RT-PCR. CRH (10-8 M) led to a moderate increase of cortisol release (145.7 +/- 20.0%) from cortical and chromaffin adrenal cells in co-culture. This effect corresponded to 41.8% of the maximal increase induced by ACTH (10-8 M). The action of CRH was completely inhibited by antalarmin. CRH, ACTH, and both CRH-R1 and CRH-R2 mRNAs are expressed in the adult human adrenal gland. CRH stimulates cortisol production in cortical and chromaffin cell co-cultures. This effect is blocked by antalarmin, a selective CRH-R1 receptor antagonist, suggesting that CRH-R1 receptors are involved in an intraadrenal CRH/ACTH control system in humans.
	
	
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        Publication type
        Article: Journal article
    
 
    
        Document type
        Scientific Article
    
 
     
    
     
     
    
    
        Language
        english
    
 
    
        Publication Year
        2000
    
 
     
    
        HGF-reported in Year
        0
    
 
    
    
        ISSN (print) / ISBN
        1359-4184
    
 
    
        e-ISSN
        1476-5578
    
 
    
     
     
	     
	 
	 
    
        Journal
        Molecular Psychiatry
    
 
	
    
        Quellenangaben
        
	    Volume: 5,  
	    Issue: 2,  
	    Pages: 137-141 
	    
	    
	
    
 
    
         
        
            Publisher
            Nature Publishing Group
        
 
         
	
         
         
         
         
         
	
         
         
         
    
         
         
         
         
         
         
         
    
        Reviewing status
        Peer reviewed
    
 
    
        Institute(s)
        Institute of Pancreatic Islet Research (IPI)
    
 
     
     
     
     
     	
    
        PubMed ID
        10822340
    
    
        Erfassungsdatum
        2000-12-31