The effect of sex and irritable bowel syndrome on HPA axis response and peripheral glucocorticoid receptor expression

Videlock, EJ, Shih, W, Adeyemo, M, Mahurkar-Joshi, S, Presson, AP, Polytarchou, C ORCID: https://orcid.org/0000-0002-1948-7934, Alberto, M, Iliopoulos, D, Mayer, EA and Chang, L, 2016. The effect of sex and irritable bowel syndrome on HPA axis response and peripheral glucocorticoid receptor expression. Psychoneuroendocrinology, 69 (July), pp. 67-76. ISSN 0306-4530

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Abstract

Background & Aims:
Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been reported in irritable bowel syndrome (IBS). Enhanced HPA axis responses have been associated with reduced glucocorticoid receptor (GR) mediated negative feedback inhibition. We aimed to study the effects of IBS status, sex, or presence of early adverse life events (EAL) on the cortisol response to corticotropin-releasing factor (CRF) and adrenocorticotropic hormone (ACTH), and on GR mRNA expression in peripheral blood mononuclear cells (PBMCs).
Methods:
Rome III+ IBS patients and healthy controls underwent CRF (1μg/kg ovine) and ACTH (250μg) stimulation tests with serial plasma ACTH and cortisol levels measured (n=116). GR mRNA levels were measured using quantitative PCR (n=143). Area under the curve (AUC) and linear mixed effects models were used to compare ACTH and cortisol response measured across time between groups.
Results:
There were divergent effects of IBS on the cortisol response to ACTH by sex. In men, IBS was associated with an increased AUC (p= 0.009), but in women AUC was blunted in IBS(p=0.006). Men also had reduced GR mRNA expression (p=0.007). Cumulative exposure to EALs was associated with an increased HPA response. Lower GR mRNA was associated with increased pituitary HPA response and increased severity of overall symptoms and abdominal pain in IBS.
Conclusion:
This study highlights the importance of considering sex in studies of IBS and the stress response in general. Our findings also provide support for PBMC GR mRNA expression as a peripheral marker of central HPA response.

Item Type:	Journal article
Publication Title:	Psychoneuroendocrinology
Creators:	Videlock, E.J., Shih, W., Adeyemo, M., Mahurkar-Joshi, S., Presson, A.P., Polytarchou, C., Alberto, M., Iliopoulos, D., Mayer, E.A. and Chang, L.
Publisher:	Elsevier for the International Society of Psycho­neuro­endocrinology
Date:	July 2016
Volume:	69
Number:	July
ISSN:	0306-4530
Identifiers:	Number Type 10.1016/j.psyneuen.2016.03.016 DOI
Divisions:	Schools > School of Science and Technology
Record created by:	Jill Tomkinson
Date Added:	15 Jul 2016 12:04
Last Modified:	09 Jun 2017 14:04
URI:	https://irep.ntu.ac.uk/id/eprint/28140

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