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This Article Full Text Full Text (PDF) All Versions of this Article: 586/2/369    most recent jphysiol.2007.146233v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Brunton, P. J. Articles by Russell, J. A. Search for Related Content PubMed PubMed Citation Articles by Brunton, P. J. Articles by Russell, J. A. Related Collections Review articles Integrative

¹ Laboratory of Neuroendocrinology, Centre for Integrative Physiology, University of Edinburgh, UK

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.

(Received 4 October 2007; accepted after revision 2 November 2007; first published online 8 November 2007)
Corresponding author J. A. Russell: Centre for Integrative Physiology, Hugh Robson Building, University of Edinburgh, George Square, Edinburgh EH8 9XD, UK. Email: j.a.russell{at}ed.ac.uk

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				Q. J. Pittman Brain adaptations for a successful pregnancy J. Physiol., January 15, 2008; 586(2): 367 - 367. [Full Text] [PDF]