Disruption of feeding behavior in CRH receptor 1-deficient mice is dependent on glucocorticoids.
Corticotropin-releasing hormone (CRH) has been found to markedly suppress food intake and reduce body weight. However, it still remains to be clarified whether those effects are mediated via either the CRH receptor 1 (CRHR1) or the CRH receptor 2 (CRHR2), or both receptor subtypes. Therefore, we investigated whether CRHR1-deficient mice (CRHR1-KO) show abnormalities in body weight and feeding behavior. CRHR1-KO and wildtype mice showed no difference in the total amount of food intake. However, there was a significant disruption in the circadian distribution of food intake: CRHR1 mutants consumed significantly more food during the light period (p<0.01). The normal diurnal pattern could be completely restored by oral administration of corticosterone 21-sulfate (5 mg/l added to the water-based liquid diet). We therefore conclude that in CRHR1-KO mice, the disruption of feeding behavior might be causally related to glucocorticoid deficiency, but that the CRHR1 is not likely to play a critical role in the basal regulation of ingestive behavior.
Müller
M B
MB
Max Planck Institute of Psychiatry, Molecular Neurogenetics, Munich, Germany.
Keck
M E
ME
Zimmermann
S
S
Holsboer
F
F
Wurst
W
W
D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000502:physiology; D002940:Circadian Rhythm / Q000502:physiology; D003345:Corticosterone / Q000097:blood / Q000494:pharmacology; D004435:Eating / Q000502:physiology; D005247:Feeding Behavior / Q000502:physiology*; D005938:Glucocorticoids / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D020033:Protein Isoforms / Q000172:deficiency* / Q000235:genetics; D018019:Receptors, Corticotropin-Releasing Hormone / Q000172:deficiency* / Q000235:genetics; D012016:Reference Values
D005938:Glucocorticoids; D020033:Protein Isoforms; D018019:Receptors, Corticotropin-Releasing Hormone; D003345:Corticosterone