Adaptive responses of the maternal hypothalamic-pituitary-adrenal axis during pregnancy and lactation

J Neuroendocrinol. 2008 Jun;20(6):764-76. doi: 10.1111/j.1365-2826.2008.01735.x.


Over the past 40 years, it has been recognised that the maternal hypothalamic-pituitary-adrenal (HPA) axis undergoes adaptations through pregnancy and lactation that might contribute to avoidance of adverse effects of stress on the mother and offspring. The extent of the global adaptations in the HPA axis has been revealed and the underlying mechanisms investigated within the last 20 years. Both basal, including the circadian rhythm, and stress-induced adrenocorticotrophic hormone and glucocorticoid secretory patterns are altered. Throughout most of pregnancy, and in lactation, these changes predominantly reflect reduced drive by the corticotropin-releasing factor (CRF) neurones in the parvocellular paraventricular nucleus (pPVN). An accompanying profound attenuation of HPA axis responses to a wide variety of psychological and physical stressors emerges after mid-pregnancy and persists until the end of lactation. Central to this suppression of stress responsiveness is reduced activation of the pPVN CRF neurones. This is consequent on the reduced effectiveness of the stimulation of brainstem afferents to these CRF neurones (for physical stressors) and of altered processing by limbic structures (for emotional stressors). The mechanism of reduced CRF neurone responses to physical stressors in pregnancy is the suppression of noradrenaline release in the PVN by an up-regulated endogenous opioid mechanism, which is induced by neuroactive steroid produced from progesterone. By contrast, in lactation suckling the young provides a neural stimulus that dampens the HPA axis circadian rhythm and reduces stress responses. Reduced noradrenergic input activity is involved in reduced stress responses in lactation, although central prolactin action also appears important. Such adaptations limit the adverse effects of excess glucocorticoid exposure on the foetus(es) and facilitate appropriate metabolic and immune responses.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Analgesics, Opioid / metabolism
  • Animals
  • Animals, Suckling
  • Arginine Vasopressin / metabolism
  • Circadian Rhythm / physiology
  • Corticotropin-Releasing Hormone / metabolism
  • Female
  • Humans
  • Hypothalamo-Hypophyseal System / physiology*
  • Lactation / physiology*
  • Pituitary-Adrenal System / physiology*
  • Pregnancy* / physiology
  • Prolactin / metabolism
  • Stress, Psychological


  • Analgesics, Opioid
  • Arginine Vasopressin
  • Prolactin
  • Corticotropin-Releasing Hormone