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Selective activation of the hypothalamic vasopressinergic system in mice deficient for the corticotropin-releasing hormone receptor 1 is dependent on glucocorticoids.
Endocrinology 141, 4262-4269 (2000)
Deficiency of CRH receptor 1 (CRHR1) severely impairs the stress response of the hypothalamic-pituitary-adrenocortical (HPA) system and reduces anxiety-related behavior in mice. Intriguingly, in mice deficient for the CRHR1 (Crhr1-/-), basal plasma levels of ACTH are normal, suggesting the presence of compensatory mechanisms for pituitary ACTH secretion. We therefore studied the impact of the hypothalamic neuropeptides arginine vasopressin (AVP) and oxytocin (OXT) on HPA system regulation in homozygous and heterozygous Crhr1 mutants under basal and different stress conditions. Basal plasma AVP concentrations were significantly elevated in Crhr1-/- mice. AVP messenger RNA expression was increased in the paraventricular nucleus of Crhr1-/- mutants together with a marked increase in AVP-like immunoreactivity in the median eminence. Administration of an AVP V1-receptor antagonist significantly decreased basal plasma ACTH levels in mutant mice. After continuous treatment with corticosterone, plasma AVP levels in homozygous Crhr1-/- mice were indistinguishable from those in wild-type littermates, thus providing evidence that glucocorticoid deficiency is the major driving force behind compensatory activation of the vasopressinergic system in Crhr1-/- mice. Neither plasma OXT levels under several different conditions nor OXT messenger RNA expression in the paraventricular nucleus were different between the genotypes. Taken together, our data reveal a selective compensatory activation of the hypothalamic vasopressinergic, but not the oxytocinergic system, to maintain basal ACTH secretion and HPA system activity in Crhr1-/- mutants.
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Publication type
Article: Journal article
Document type
Scientific Article
Language
english
Publication Year
2000
HGF-reported in Year
0
ISSN (print) / ISBN
0013-7227
e-ISSN
1945-7170
Journal
Endocrinology
Quellenangaben
Volume: 141,
Issue: 11,
Pages: 4262-4269
Publisher
Endocrine Society
Publishing Place
Chevy Chase, Md.
Reviewing status
Peer reviewed
Institute(s)
Institute of Developmental Genetics (IDG)
POF-Topic(s)
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s)
Genetics and Epidemiology
PSP Element(s)
G-520600-001
Erfassungsdatum
2004-12-31