Reduced hypothalamo-pituitary-adrenal axis stress responses in late pregnancy: central opioid inhibition and noradrenergic mechanisms.
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.
Russell
John A
JA
Laboratory of Neuroendocrinology, Centre for Integrative Physiology, University of Edinburgh, Edinburgh, United Kingdom. j.a.russell@ed.ac.uk
Douglas
Alison J
AJ
Brunton
Paula J
PJ
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000701:Analgesics, Opioid / Q000378:metabolism*; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D053583:Interleukin-1beta / Q000378:metabolism; D009270:Naloxone / Q000378:metabolism; D009292:Narcotic Antagonists / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000502:physiology*; D011247:Pregnancy; D051381:Rats; D013315:Stress, Psychological
D000701:Analgesics, Opioid; D053583:Interleukin-1beta; D009292:Narcotic Antagonists; D009270:Naloxone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D009638:Norepinephrine