Document Detail

Reduced hypothalamo-pituitary-adrenal axis stress responses in late pregnancy: central opioid inhibition and noradrenergic mechanisms.
MedLine Citation:
PMID:  19120138     Owner:  NLM     Status:  MEDLINE    
In late pregnancy, the hypothalamo-pituitary-adrenal (HPA) axis is less responsive to a range of psychological and physical stressors as a result of reduced central drive to the corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus (PVN). Most stressors activate the brain stem noradrenergic system, which innervates the majority of networks involved in regulating stress responses, including the PVN. Forced swimming, systemic interleukin-1beta (IL-1beta), and cholecystokinin (CCK) all activate brain stem noradrenergic cell groups, stimulate noradrenaline release in the PVN, and activate the HPA axis in nonpregnant rats. However, in late pregnancy we have shown that forced swimming and IL-1beta fail to evoke noradrenaline release in the PVN and hence HPA axis responses are suppressed. HPA axis responses to IL-1beta and CCK can be reinstated in pregnant rats by systemic administration of the opioid receptor antagonist naloxone, and when infused directly into the PVN, naloxone restores noradrenaline release in the PVN following IL-1beta treatment. Adrenaline release into the blood following stress is also attenuated in late pregnancy, despite increased adrenomedullary expression of tyrosine hydroxylase mRNA at this time. This review describes the mechanisms underlying attenuated HPA axis stress responses in pregnancy, focusing on the role of endogenous opioids and the central noradrenergic system.
John A Russell; Alison J Douglas; Paula J Brunton
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Annals of the New York Academy of Sciences     Volume:  1148     ISSN:  1749-6632     ISO Abbreviation:  Ann. N. Y. Acad. Sci.     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2009-01-05     Completed Date:  2009-01-23     Revised Date:  2009-02-13    
Medline Journal Info:
Nlm Unique ID:  7506858     Medline TA:  Ann N Y Acad Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  428-38     Citation Subset:  IM    
Laboratory of Neuroendocrinology, Centre for Integrative Physiology, University of Edinburgh, Edinburgh, United Kingdom.
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MeSH Terms
Adrenocorticotropic Hormone / metabolism
Analgesics, Opioid / metabolism*
Corticotropin-Releasing Hormone / metabolism
Hypothalamo-Hypophyseal System / physiology*
Interleukin-1beta / metabolism
Naloxone / metabolism
Narcotic Antagonists / metabolism
Norepinephrine / metabolism*
Paraventricular Hypothalamic Nucleus / metabolism
Pituitary-Adrenal System / physiology*
Stress, Psychological*
Grant Support
//Biotechnology and Biological Sciences Research Council
Reg. No./Substance:
0/Analgesics, Opioid; 0/Interleukin-1beta; 0/Narcotic Antagonists; 465-65-6/Naloxone; 51-41-2/Norepinephrine; 9002-60-2/Adrenocorticotropic Hormone; 9015-71-8/Corticotropin-Releasing Hormone

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