Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in irritable bowel syndrome

Authors

  • L. Chang,

    1. Center for Neurobiology of Stress, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
    2. Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
    3. VA GLA Healthcare System, Los Angeles, CA, USA
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  • S. Sundaresh,

    1. Institute for Genomics and Bioinformatics, University of California, Irvine, CA, USA
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  • J. Elliott,

    1. Center for HIV Prevention Research, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
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  • P. A. Anton,

    1. Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
    2. Center for HIV Prevention Research, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
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  • P. Baldi,

    1. Institute for Genomics and Bioinformatics, University of California, Irvine, CA, USA
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  • A. Licudine,

    1. Center for Neurobiology of Stress, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
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  • M. Mayer,

    1. Center for Neurobiology of Stress, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
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  • T. Vuong,

    1. Center for Neurobiology of Stress, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
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  • M. Hirano,

    1. Center for Neurobiology of Stress, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
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  • B. D. Naliboff,

    1. Center for Neurobiology of Stress, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
    2. Department of Psychiatry & Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
    3. Division of Mental Health, VA GLA Healthcare System, Los Angeles, CA, USA
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  • V. Z. Ameen,

    1. GlaxoSmithKline Research and Development, GI Discovery Medicine, Research Triangle Park, NC, USA
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  • E. A. Mayer

    1. Center for Neurobiology of Stress, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
    2. Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
    3. Department of Psychiatry & Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
    4. Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
    5. Brain Research Institute, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
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  • Present address: Vanessa Z. Ameen, Prometheus Laboratories Inc., Carroll Park Drive, San Diego, CA 92121, USA.

Lin Chang MD, Center for Neurobiology of Stress, VA GLAHS, Building 115, Room 223, 11301 Wilshire Blvd, Los Angeles, CA 90073, USA.
Tel: +1 310 312 9276; fax: +1 310 794 2864; e-mail: linchang@ucla.edu

Abstract

Abstract  Enhanced stress responsiveness has been implicated as a potential mechanism contributing to the pathophysiology of irritable bowel syndrome (IBS), and should be reflected in altered function of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system. Both of these systems can modulate mucosal immune function. The aims of this study were: (i) to characterize the basal circadian rhythm of adrenocorticotropin hormone (ACTH) and cortisol in IBS vs healthy controls; (ii) to compare stimulated ACTH, cortisol and noradrenaline responses to a pelvic visceral stressor (sigmoidoscopy) in IBS and controls; and (iii) to correlate neuroendocrine responses with colonic mucosal cytokine expression and symptoms in IBS. Two separate studies were conducted in women. In Study 1, basal cortisol levels were analysed in 41 IBS and 25 controls using 24-h collections of plasma ACTH and cortisol (q10 min sampling). In Study 2, 10 IBS patients with diarrhoea (IBS-D) and 10 controls underwent sigmoidoscopy with measurements of stimulated neuroendocrine responses and cytokine mRNA expression in colonic tissue. Basal ACTH levels were significantly blunted (< 0.05), while basal and stimulated plasma cortisol levels were higher in patients. Basal cortisol levels prior to an experimental visceral stressor positively correlated with anxiety symptoms (< 0.004), but not IBS symptoms. Irritable bowel syndrome patients with diarrhoea had significantly decreased mRNA expression of mucosal cytokines [interleukin (IL)-2, IL-6] in the sigmoid colon vs controls (< 0.05). Although dysregulations in stress-responsive systems such as the HPA axis and mucosal immune function are demonstrated in IBS, they do not appear to have a primary role in modulating IBS severity and abdominal pain.

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