Control of the hypothalamo-pituitary-adrenal axis in the neonatal period: adrenocorticotropin and corticosterone stress responses dissociate in vasopressin-deficient brattleboro rats

Endocrinology. 2008 May;149(5):2576-83. doi: 10.1210/en.2007-1537. Epub 2008 Feb 14.


In adulthood the hypothalamo-pituitary-adrenal axis is controlled by both CRH and arginine vasopressin (AVP). However, in neonates CRH secretion is very low, whereas AVP secretion is fully functional. This suggests that the role of AVP is more pronounced in young than in adult rats. We investigated the role of AVP by studying stress responses in 5, 10, and 20-d-old AVP-deficient Brattleboro rats. Two different stressors were applied: 24-h maternal separation and Hypnorm Grove Oxford UK injections. In heterozygous controls (that do express AVP), both stressors increased plasma ACTH and corticosterone. The ACTH stress response disappeared in AVP-deficient rats, demonstrating that during the perinatal period, the secretion of this hormone is controlled by AVP. Surprisingly, corticosterone responses remained intact in AVP-deficient rats. Similar findings were obtained after 1-, 4-, 12-, and 24-h long maternal separations. Thus, preserved corticosterone stress responses were not explained by changes in the timing of ACTH secretion. In vitro experiments suggested that the dissociation of ACTH and corticosterone stress responses can only be partly explained by higher ACTH responsiveness of the adrenal cortex in AVP-deficient rats. Together, our results show that in neonatal periods, AVP is crucial for the expression of ACTH stress responses, but neither AVP nor ACTH is necessary for the induction of corticosterone stress responses. Discrepant ACTH and corticosterone stress responses may reflect compensatory mechanisms activated by AVP deficiency, but disparate findings suggest that they rather depict a neonate-specific mechanism of hypothalamo-pituitary-adrenal-axis control.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenocorticotropic Hormone / blood*
  • Adrenocorticotropic Hormone / physiology
  • Age Factors
  • Animals
  • Animals, Genetically Modified
  • Animals, Newborn
  • Butyrophenones / pharmacology
  • Corticosterone / blood*
  • Corticosterone / physiology
  • Corticotropin-Releasing Hormone / genetics
  • Corticotropin-Releasing Hormone / metabolism
  • Drug Combinations
  • Female
  • Fentanyl / pharmacology
  • Genotype
  • Hypothalamo-Hypophyseal System / metabolism
  • Hypothalamo-Hypophyseal System / physiology*
  • Male
  • Maternal Deprivation
  • Pituitary-Adrenal System / metabolism
  • Pituitary-Adrenal System / physiology*
  • Rats
  • Rats, Brattleboro
  • Stress, Physiological / blood*
  • Stress, Physiological / genetics
  • Stress, Physiological / physiopathology
  • Time Factors
  • Vasopressins / genetics*


  • Butyrophenones
  • Drug Combinations
  • Vasopressins
  • Hypnorm
  • Adrenocorticotropic Hormone
  • Corticotropin-Releasing Hormone
  • Fentanyl
  • Corticosterone