CRH receptor type 1 mediates continual hypoxia-induced changes of immunoreactive prolactin and prolactin mRNA expression in rat pituitary

Horm Behav. 2006 Feb;49(2):181-9. doi: 10.1016/j.yhbeh.2005.06.004. Epub 2005 Aug 15.


We have reported that, in rats, hypoxia (10.8% O2) stimulates prolactin (PRL) release from the pituitary. This study is designed to compare the response of pituitary PRL to acute hypoxia (AH), continual hypoxia (CH), intermittent hypoxia (IH), cold, and restraint, individually and combined with hypoxia. This study also investigates the involvement of the corticotropin-releasing hormone receptor 1 (CRH R1) in the hypoxia-induced PRL response. Hypoxia was induced by exposing the rats to high altitudes of 2 km (16.0% O2) or 5 km (10.8% O2). The PRL levels in the pituitary (iPRL) and in plasma (pPRL) were measured by immunocytochemistry and RIA assay, respectively. The acute hypoxia of 5 km for 2-24 h caused a biphasic change (early decrease and late increase) of PRL. Both CH and IH at 2 or 5 km for 1-5 days markedly increased pPRL but decreased iPRL. Continual severe hypoxia (10.8% O2) for periods of 10, 15, and 25 days significantly enhanced pPRL but this effect was less marked at the lower altitude (16.0% O2) and did not occur during intermittent hypoxia (at both altitudes). The increased pPRL was significantly enhanced by restraint, restraint + hypoxia, hypoxia, and cold + hypoxia exposure. Treatment with a CRH R1 antagonist (CP-154,526) reversed hypoxia-decreased immunoreactive PRL and upregulated PRLmRNA in the pituitary. The data suggest that both CH and IH can stimulate rat PRL release in a time-course- and intensity-dependent manner. However, compared to the relatively low CH-induced response, restraint induced a more powerful response than either cold or hypoxia alone. CRH R1 mediates PRL secretion and PRL mRNA expression in the pituitary under hypoxic exposure. Hypoxia-enhanced PRL response over the lifespan may play a significant role in adaptation to an extreme environment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenalectomy
  • Adrenocorticotropic Hormone / physiology
  • Animals
  • Cold Temperature
  • Corticotropin-Releasing Hormone / blood
  • Hypoxia / metabolism*
  • Immunohistochemistry
  • Male
  • Paraventricular Hypothalamic Nucleus / physiology
  • Peptide Fragments / blood
  • Pituitary Gland / metabolism*
  • Prolactin / biosynthesis
  • Prolactin / blood*
  • Pyrimidines / pharmacology
  • Pyrroles / pharmacology
  • RNA, Messenger / biosynthesis*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Corticotropin-Releasing Hormone / metabolism*
  • Restraint, Physical
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stress, Psychological / metabolism


  • CP 154526
  • Peptide Fragments
  • Pyrimidines
  • Pyrroles
  • RNA, Messenger
  • Receptors, Corticotropin-Releasing Hormone
  • CRF receptor type 1
  • Adrenocorticotropic Hormone
  • Prolactin
  • Corticotropin-Releasing Hormone
  • corticotropin releasing hormone (9-41)