Projects per year
Abstract / Description of output
In virgin rats, systemic administration of interleukin-1β (IL-1β, to mimic infection), increases oxytocin secretion and the firing rate of oxytocin neurones in the supraoptic nucleus (SON). However, in late pregnancy stimulated oxytocin secretion is inhibited by an endogenous opioid mechanism, preserving the expanded neurohypophysial oxytocin stores for parturition and minimising risk of preterm labour. Central levels of the neuroactive metabolite of progesterone, allopregnanolone, increase during pregnancy and allopregnanolone acting on GABA(A) receptors on oxytocin neurones enhances inhibitory transmission. Here we tested whether allopregnanolone induces opioid inhibition of the oxytocin system in response to IL-1β in late pregnancy. Inhibition of 5α-reductase (an allopregnanolone-synthesising enzyme) with finasteride potentiated IL-1β-evoked oxytocin secretion in late pregnant rats, while allopregnanolone reduced the oxytocin response in virgin rats. IL-1β increased the number of magnocellular neurones in the SON and paraventricular nucleus (PVN) expressing Fos (an indicator of neuronal activation) in virgin, but not pregnant rats. In immunoreactive oxytocin neurones in the SON and PVN, finasteride increased IL-1β-induced Fos expression in pregnant rats. Conversely, allopregnanolone reduced the number of magnocellular oxytocin neurones activated by IL-1β in virgin rats. Treatment with naloxone (an opioid antagonist) greatly enhanced the oxytocin response to IL-1β in pregnancy, and finasteride did not enhance this effect, indicating that allopregnanolone and the endogenous opioid mechanisms do not act independently. Indeed allopregnanolone induced opioid inhibition over oxytocin responses to IL-1β in virgin rats. Thus, in late pregnancy allopregnanolone induces opioid inhibition over magnocellular oxytocin neurones and hence on oxytocin secretion in response to immune challenge. This mechanism will minimise the risk of preterm labour and prevent depletion of neurohypophysial oxytocin stores, required for parturition.
Original language | English |
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Pages (from-to) | 690-700 |
Journal | Journal of Neuroendocrinology |
Volume | 24 |
Issue number | 4 |
Early online date | 17 Feb 2012 |
DOIs | |
Publication status | Published - 2012 |
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Dive into the research topics of 'Allopregnanolone and induction of endogenous opioid inhibition of oxytocin responses to immune stress in pregnant rats'. Together they form a unique fingerprint.Projects
- 1 Finished
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Brain mechanisms that underlie reduced corticotropin releasing hormone neuron stress responses in pregnancy
Russell, J. & Douglas, A.
1/03/03 → 28/02/06
Project: Research
Activities
- 1 Participation in conference
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13th World Congress on Neurohypophysial Hormones
Paula Brunton (Invited speaker)
8 Apr 2019 → 11 Apr 2019Activity: Participating in or organising an event types › Participation in conference