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

Jens Preil, Marianne B. Müller, Angela Gesing, Johannes M H M Reul, Inge Sillaber, Marcel M. Van Gaalen, Jobst Landgrebe, Florian Holsboer, Mary Stenzel-Poore, Wolfgang Wurst

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

Recent investigations in mouse lines either deficient for the CRH receptor 1 (CRHR1) or 2 (CRHR2) suggest that the CRH neuronal system may comprise two separate pathways that can be coordinately and inversely activated in stress-induced hypothalamic-pituitary-adrenal (HPA) response and anxiety-like behavior. We generated mice deficient for both CRHR1 (Crhr1-/-) and CRHR2 (Crhr2-/-) to investigate the HPA system regulation in the absence of known functionally active CRH receptors under basal conditions and in response to different ethologically relevant stressors. To elucidate possible gene dose effects on the action of both CRH receptors, our analysis included heterozygous and homozygous CRHR1- or CRHR2-deficient mice, mutants lacking both CRH receptors, compound mutants with homozygous and heterozygous deficiency for either of the receptors, and their wild-type littermates. Both male and female Crhr1-/- Crhr2-/- mutants were viable, fertile, and indistinguishable in size from wild-type littermates. We show that the endocrine phenotype of mice lacking both CRHRs is dominated by the functional loss of CRHR1. CRHR2 does not compensate for CRHR1 deficiency, nor does the lack of CRHR2 exacerbate the CRHR1-dependent impairment of the HPA system function. Within the intraadrenal CRH/ACTH system, our data suggest different roles for CRHR1 and CRHR2 in fine-tuning of adrenocortical corticosterone release.

Original languageEnglish (US)
Pages (from-to)4946-4955
Number of pages10
JournalEndocrinology
Volume142
Issue number11
DOIs
StatePublished - 2001

Fingerprint

Corticotropin-Releasing Hormone Receptors
Pituitary-Adrenal System
Corticosterone
Adrenocorticotropic Hormone
Anxiety

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Preil, J., Müller, M. B., Gesing, A., Reul, J. M. H. M., Sillaber, I., Van Gaalen, M. M., ... Wurst, W. (2001). Regulation of the hypothalamic-pituitary-adrenocortical system in mice deficient for CRH receptors 1 and 2. Endocrinology, 142(11), 4946-4955. https://doi.org/10.1210/en.142.11.4946

Regulation of the hypothalamic-pituitary-adrenocortical system in mice deficient for CRH receptors 1 and 2. / Preil, Jens; Müller, Marianne B.; Gesing, Angela; Reul, Johannes M H M; Sillaber, Inge; Van Gaalen, Marcel M.; Landgrebe, Jobst; Holsboer, Florian; Stenzel-Poore, Mary; Wurst, Wolfgang.

In: Endocrinology, Vol. 142, No. 11, 2001, p. 4946-4955.

Research output: Contribution to journalArticle

Preil, J, Müller, MB, Gesing, A, Reul, JMHM, Sillaber, I, Van Gaalen, MM, Landgrebe, J, Holsboer, F, Stenzel-Poore, M & Wurst, W 2001, 'Regulation of the hypothalamic-pituitary-adrenocortical system in mice deficient for CRH receptors 1 and 2', Endocrinology, vol. 142, no. 11, pp. 4946-4955. https://doi.org/10.1210/en.142.11.4946
Preil, Jens ; Müller, Marianne B. ; Gesing, Angela ; Reul, Johannes M H M ; Sillaber, Inge ; Van Gaalen, Marcel M. ; Landgrebe, Jobst ; Holsboer, Florian ; Stenzel-Poore, Mary ; Wurst, Wolfgang. / Regulation of the hypothalamic-pituitary-adrenocortical system in mice deficient for CRH receptors 1 and 2. In: Endocrinology. 2001 ; Vol. 142, No. 11. pp. 4946-4955.
@article{fae61d66bd7542b2a9db9a2d944bab2f,
title = "Regulation of the hypothalamic-pituitary-adrenocortical system in mice deficient for CRH receptors 1 and 2",
abstract = "Recent investigations in mouse lines either deficient for the CRH receptor 1 (CRHR1) or 2 (CRHR2) suggest that the CRH neuronal system may comprise two separate pathways that can be coordinately and inversely activated in stress-induced hypothalamic-pituitary-adrenal (HPA) response and anxiety-like behavior. We generated mice deficient for both CRHR1 (Crhr1-/-) and CRHR2 (Crhr2-/-) to investigate the HPA system regulation in the absence of known functionally active CRH receptors under basal conditions and in response to different ethologically relevant stressors. To elucidate possible gene dose effects on the action of both CRH receptors, our analysis included heterozygous and homozygous CRHR1- or CRHR2-deficient mice, mutants lacking both CRH receptors, compound mutants with homozygous and heterozygous deficiency for either of the receptors, and their wild-type littermates. Both male and female Crhr1-/- Crhr2-/- mutants were viable, fertile, and indistinguishable in size from wild-type littermates. We show that the endocrine phenotype of mice lacking both CRHRs is dominated by the functional loss of CRHR1. CRHR2 does not compensate for CRHR1 deficiency, nor does the lack of CRHR2 exacerbate the CRHR1-dependent impairment of the HPA system function. Within the intraadrenal CRH/ACTH system, our data suggest different roles for CRHR1 and CRHR2 in fine-tuning of adrenocortical corticosterone release.",
author = "Jens Preil and M{\"u}ller, {Marianne B.} and Angela Gesing and Reul, {Johannes M H M} and Inge Sillaber and {Van Gaalen}, {Marcel M.} and Jobst Landgrebe and Florian Holsboer and Mary Stenzel-Poore and Wolfgang Wurst",
year = "2001",
doi = "10.1210/en.142.11.4946",
language = "English (US)",
volume = "142",
pages = "4946--4955",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "The Endocrine Society",
number = "11",

}

TY - JOUR

T1 - Regulation of the hypothalamic-pituitary-adrenocortical system in mice deficient for CRH receptors 1 and 2

AU - Preil, Jens

AU - Müller, Marianne B.

AU - Gesing, Angela

AU - Reul, Johannes M H M

AU - Sillaber, Inge

AU - Van Gaalen, Marcel M.

AU - Landgrebe, Jobst

AU - Holsboer, Florian

AU - Stenzel-Poore, Mary

AU - Wurst, Wolfgang

PY - 2001

Y1 - 2001

N2 - Recent investigations in mouse lines either deficient for the CRH receptor 1 (CRHR1) or 2 (CRHR2) suggest that the CRH neuronal system may comprise two separate pathways that can be coordinately and inversely activated in stress-induced hypothalamic-pituitary-adrenal (HPA) response and anxiety-like behavior. We generated mice deficient for both CRHR1 (Crhr1-/-) and CRHR2 (Crhr2-/-) to investigate the HPA system regulation in the absence of known functionally active CRH receptors under basal conditions and in response to different ethologically relevant stressors. To elucidate possible gene dose effects on the action of both CRH receptors, our analysis included heterozygous and homozygous CRHR1- or CRHR2-deficient mice, mutants lacking both CRH receptors, compound mutants with homozygous and heterozygous deficiency for either of the receptors, and their wild-type littermates. Both male and female Crhr1-/- Crhr2-/- mutants were viable, fertile, and indistinguishable in size from wild-type littermates. We show that the endocrine phenotype of mice lacking both CRHRs is dominated by the functional loss of CRHR1. CRHR2 does not compensate for CRHR1 deficiency, nor does the lack of CRHR2 exacerbate the CRHR1-dependent impairment of the HPA system function. Within the intraadrenal CRH/ACTH system, our data suggest different roles for CRHR1 and CRHR2 in fine-tuning of adrenocortical corticosterone release.

AB - Recent investigations in mouse lines either deficient for the CRH receptor 1 (CRHR1) or 2 (CRHR2) suggest that the CRH neuronal system may comprise two separate pathways that can be coordinately and inversely activated in stress-induced hypothalamic-pituitary-adrenal (HPA) response and anxiety-like behavior. We generated mice deficient for both CRHR1 (Crhr1-/-) and CRHR2 (Crhr2-/-) to investigate the HPA system regulation in the absence of known functionally active CRH receptors under basal conditions and in response to different ethologically relevant stressors. To elucidate possible gene dose effects on the action of both CRH receptors, our analysis included heterozygous and homozygous CRHR1- or CRHR2-deficient mice, mutants lacking both CRH receptors, compound mutants with homozygous and heterozygous deficiency for either of the receptors, and their wild-type littermates. Both male and female Crhr1-/- Crhr2-/- mutants were viable, fertile, and indistinguishable in size from wild-type littermates. We show that the endocrine phenotype of mice lacking both CRHRs is dominated by the functional loss of CRHR1. CRHR2 does not compensate for CRHR1 deficiency, nor does the lack of CRHR2 exacerbate the CRHR1-dependent impairment of the HPA system function. Within the intraadrenal CRH/ACTH system, our data suggest different roles for CRHR1 and CRHR2 in fine-tuning of adrenocortical corticosterone release.

UR - http://www.scopus.com/inward/record.url?scp=17944379995&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=17944379995&partnerID=8YFLogxK

U2 - 10.1210/en.142.11.4946

DO - 10.1210/en.142.11.4946

M3 - Article

VL - 142

SP - 4946

EP - 4955

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 11

ER -