The parvocellular vasopressinergic system and responsiveness of the hypothalamic pituitary adrenal axis during chronic stress

Prog Brain Res. 2008;170:29-39. doi: 10.1016/S0079-6123(08)00403-2.


Vasopressin (VP) secreted from parvocellular neurons of the hypothalamic paraventricular nucleus (PVN) stimulates pituitary adrenocorticotropic hormone (ACTH) secretion, through interaction with receptors of the V1b subtype (V1bR) in the pituitary corticotroph, mainly by potentiating the stimulatory effects of corticotrophin-releasing hormone (CRH). Chronic stress paradigms associated with corticotroph hyperresponsiveness lead to preferential expression of hypothalamic VP over CRH and upregulation of pituitary V1bR, suggesting that VP has a primary role during adaptation of the hypothalamic pituitary adrenal (HPA) axis to long-term stimulation. However, studies using pharmacological or genetic ablation of V1bR have shown that VP is required for full ACTH responses to some stressors, but not for the sensitization of ACTH responses to a novel stress observed during chronic stress. Studies using minipump infusion of a peptide V1 antagonist in long-term adrenalectomized rats have revealed that VP mediates proliferative responses in the pituitary. Nevertheless, only a minor proportion of cells undergoing mitogenesis co-express markers for differentiated corticotrophs or precursors, suggesting that new corticotrophs are recruited from yet undifferentiated cells. The overall evidence supports a limited role of VP regulating acute ACTH responses to some acute stressors and points to cell proliferation and pituitary remodelling as alternative roles for the marked increases in parvocellular vasopressinergic activity during prolonged activation of the HPA axis.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Adrenocorticotropic Hormone / metabolism
  • Anesthetics / therapeutic use
  • Animals
  • Chronic Disease
  • Corticotropin-Releasing Hormone / metabolism
  • Humans
  • Hypothalamo-Hypophyseal System / physiopathology*
  • Paraventricular Hypothalamic Nucleus / physiology
  • Pituitary-Adrenal System / physiopathology*
  • Receptors, Corticotropin / physiology
  • Receptors, Vasopressin / physiology
  • Rodentia
  • Stress, Psychological / physiopathology
  • Vasopressins / metabolism*


  • Anesthetics
  • Receptors, Corticotropin
  • Receptors, Vasopressin
  • Vasopressins
  • Adrenocorticotropic Hormone
  • Corticotropin-Releasing Hormone