Keeping oxytocin neurons under control during stress in pregnancy.
Oxytocin synthesised by magnocellular neurons in the supraoptic and paraventricular nuclei plays an important role in mammalian parturition. Accordingly, in late pregnant rats, oxytocin neurons are restrained from premature activation and stimulated oxytocin secretion is inhibited, preserving the expanded neurohypophysial oxytocin stores for parturition. A wide range of stressors stimulate oxytocin secretion in the rat. Some physical stressors, in particular immune challenge with systemic interleukin-1beta (IL-1beta, a cytokine that mimics infection) signal to magnocellular oxytocin neurons via brainstem noradrenergic neurons. Afferents relaying information from the uterus and birth canal also converge onto brainstem noradrenergic neurons and are robustly activated at parturition. Thus, quiescence of these inputs may be important in minimising the risk of preterm labour. Focussing on an immune challenge model (since infection is a major cause of preterm labour in women), we have found that the responsiveness of oxytocin neurons to IL-1beta is markedly suppressed in late pregnancy. Here we discuss the mechanisms involved, which include induction of central inhibitory opioid tone by the progesterone neurosteroid metabolite, allopregnanolone, and act to prevent activation of oxytocin neurons by inappropriate stimuli at the end of pregnancy.
Brunton
Paula J
PJ
Laboratory of Neuroendocrinology, Centre for Integrative Physiology, University of Edinburgh, Scotland, UK.
Russell
John A
JA
D000818:Animals; D002766:Cholecystokinin / Q000502:physiology; D005260:Female; D006706:Homeostasis; D008322:Mammals; D009215:Myometrium / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D010121:Oxytocin / Q000502:physiology*; D010286:Paraventricular Hypothalamic Nucleus / Q000502:physiology; D036801:Parturition / Q000502:physiology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology / Q000523:psychology; D011374:Progesterone / Q000502:physiology; D051381:Rats; D013315:Stress, Psychological / Q000503:physiopathology; D013495:Supraoptic Nucleus / Q000502:physiology*; D014599:Uterus / Q000502:physiology
D011374:Progesterone; D010121:Oxytocin; D002766:Cholecystokinin