Attenuated hypothalamo‐pituitary‐adrenal axis responses to immune challenge during pregnancy: the neurosteroid–opioid connection
In late pregnancy maternal hypothalamo‐pituitary‐adrenal (HPA) axis responses to emotional and physical stressors are attenuated. This is expected to minimize the detrimental programming effects of glucocorticoid exposure on the fetuses. We have utilized a model of immune challenge, systemic adminis...
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Published in | The Journal of physiology Vol. 586; no. 2; pp. 369 - 375 |
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Main Authors | , |
Format | Journal Article |
Language | English |
Published |
Oxford, UK
Blackwell Publishing Ltd
15.01.2008
Blackwell Science Inc |
Subjects | |
Online Access | Get full text |
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Summary: | In late pregnancy maternal hypothalamo‐pituitary‐adrenal (HPA) axis responses to emotional and physical stressors are attenuated. This is expected to minimize the detrimental programming effects of glucocorticoid exposure on the fetuses. We have utilized a model of immune challenge, systemic administration of interleukin‐1β (IL‐1β), to investigate the underlying mechanisms. Intravenous IL‐1β activates corticotropin‐releasing hormone (CRH) neurones in the parvocellular division of the paraventricular nucleus (pPVN) via noradrenergic (A2 cell group) neurones in the nucleus tractus solitarii (NTS). Despite comparable activation of these brainstem neurones by IL‐1β in virgin and in late pregnant rats, pPVN CRH neurones are activated only in virgin rats. As a consequence IL‐1β fails to evoke ACTH and corticosterone secretion in late pregnant rats, in contrast to virgin rats. Suppressed responsiveness of the CRH neurones, and hence the HPA axis, following IL‐1β in late pregnancy is explained by presynaptic inhibition of noradrenaline release in the pPVN, due to increased endogenous enkephalin and μ‐opioid receptor production in brainstem NTS neurones. The factor that signals to the brain the pregnancy status of the animal and stimulates opioid production in the brainstem is allopregnanolone, a neurosteroid metabolite of progesterone. The supporting evidence for these mechanisms is discussed. |
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Bibliography: | The Journal of Physiology Symposium on Brain adaptations for a successful pregnancy, IBRO World Congress of Neuroscience, Melbourne, Australia, 16 July 2007. It was commissioned by the Editorial Board and reflects the views of the authors. This report was presented at ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-3 ObjectType-Review-1 This report was presented at The Journal of Physiology Symposium on Brain adaptations for a successful pregnancy, IBRO World Congress of Neuroscience, Melbourne, Australia, 16 July 2007. It was commissioned by the Editorial Board and reflects the views of the authors. |
ISSN: | 0022-3751 1469-7793 |
DOI: | 10.1113/jphysiol.2007.146233 |