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Regulation of the hypothalamic-pituitary-adrenocortical system in mice deficient for CRH receptors 1 and 2

J Preil1, M B Müller, A Gesing

  • 1Max Planck Institute of Psychiatry, 80804 Munich, Germany.

Endocrinology
|October 19, 2001
PubMed

Insights

Mice lacking both corticotropin-releasing hormone receptors (CRHR1 and CRHR2) show HPA axis dysfunction primarily due to CRHR1 loss. CRHR2 does not compensate for CRHR1 deficiency in stress response.

Area of Science:

  • Neuroendocrinology
  • Behavioral Neuroscience
  • Genetics

Background:

  • The corticotropin-releasing hormone (CRH) system regulates stress response and behavior.
  • Previous studies suggest CRH receptor 1 (CRHR1) and CRH receptor 2 (CRHR2) may mediate separate pathways.
  • Understanding the combined roles of CRHR1 and CRHR2 is crucial for stress response research.

Purpose of the Study:

  • To investigate the function of the hypothalamic-pituitary-adrenal (HPA) axis in mice lacking both CRHR1 and CRHR2.
  • To determine if CRHR2 can compensate for CRHR1 deficiency or vice versa.
  • To explore gene dose effects on CRH receptor function under basal and stress conditions.

Main Methods:

  • Generation of mice deficient for both CRHR1 and CRHR2 (Crhr1(-/-)Crhr2(-/-)).
  • Analysis included homozygous and heterozygous single and compound receptor knockouts, and wild-type littermates.
  • Assessment of HPA system regulation under basal conditions and in response to ethologically relevant stressors.

Main Results:

  • Mice lacking both CRHR1 and CRHR2 were viable and fertile.
  • The endocrine phenotype was predominantly influenced by the loss of CRHR1.
  • CRHR2 deficiency did not exacerbate CRHR1-dependent HPA system impairments, nor did it compensate for CRHR1 loss.
  • CRHR1 and CRHR2 appear to have distinct roles in regulating intraadrenal CRH/ACTH and corticosterone release.

Conclusions:

  • CRHR1 plays a dominant role in the HPA axis regulation compared to CRHR2.
  • CRHR2 does not functionally compensate for CRHR1 in the absence of stress.
  • CRHR1 and CRHR2 have differential roles in the fine-tuning of the stress response within the adrenal gland.

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