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Expression of corticotropin releasing hormone receptors type I and type II mRNA in suicide victims and controls

Molecular Psychiatry volume 6, pages 540–546 (2001)Cite this article

Abstract

Corticotropin-releasing hormone (CRH) is a key neuroendocrine factor implementing endocrine, immune and behavioral responses to stress. CRH exerts its action through two major receptors, CRH-R1 and CRH-R2. Recently novel non-peptidic antagonists directed against CRH-R1 or CRH-R2 have been proposed as promising agents in the treatment of depression, anxiety and eating disorder. However, so far the CRH-receptor system has not been widely studied in humans. Therefore, we employed quantitative TaqMan PCR to analyze the expression and distribution of both CRH-R1 and CRH-R2 in human brain tissue and peripheral organs. Furthermore the expression of CRH receptors was analyzed for the first time in pituitaries of suicide victims by in situ hybridization and quantitative PCR. Our data demonstrated a different expression pattern in humans as compared to rodents. Both CRH-R1 and CRH-R2 were expressed in high amounts in the brain with the strongest expression in the pituitary. As described in rodents, however the CRH-R1 in human was the predominant receptor in the brain (82.7 ± 11.0%), whilst CRH-R2 was the predominant receptor in peripheral organs (77.0 ± 15.8%). There was a shift in the ratio of CRH-R1/R2 in the pituitaries of suicide victims. In conclusion, both CRH-R1 and CRH-R2 are widely expressed in human tissues with a distribution substantially different from rodents. Strong expression of both CRH-R1 and CRH-R2 in human pituitaries suggests that particularly under stress, activation of the HPA axis can be maintained through both receptors.

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Acknowledgements

This study was supported by grants of the Deutsche Forschungsgemeinschaft (BO 1141/7-1) and Deutsche Krebshilfe (10-1662-RE2) to SRB and Japan Society for the Promotion of Science to NH. We are grateful to Peter Bongiorno. JL is supported by NIH grants U01GM61394, K30HL04526, R01DK58851 and by awards from the Dana and Stanley Foundations. M-LW is supported by NIH grant P50AT00151 and by a NARSAD award.

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Authors and Affiliations

  1. Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, 20892, Maryland, USA

    N Hiroi, M Young, G P Chrousos & S R Bornstein

  2. National Institute of Mental Health, National Institutes of Health, Bethesda, 20892, Maryland, USA

    C Park & P W Gold

  3. Laboratory of Pharmacogenomics, Neuropsychiatric Institute, University of California, Los Angeles, School of Medicine, Los Angeles, 90095–1761, CA, USA

    M L Wong & J Licinio

  4. Department of Endocrinology, Heinrich-Heine University, Düsseldorf, Germany

    S R Bornstein

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  1. N Hiroi
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Correspondence to S R Bornstein.

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Hiroi, N., Wong, M., Licinio, J. et al. Expression of corticotropin releasing hormone receptors type I and type II mRNA in suicide victims and controls. Mol Psychiatry 6, 540–546 (2001). https://doi.org/10.1038/sj.mp.4000908

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  • DOI: https://doi.org/10.1038/sj.mp.4000908

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