Urocortin 2-deficient mice exhibit gender-specific alterations in circadian hypothalamus-pituitary-adrenal axis and depressive-like behavior.
Gender differences in hypothalamus-pituitary-adrenal (HPA) axis activation and the prevalence of mood disorders are well documented. Urocortin 2, a recently identified member of the corticotropin-releasing factor family, is expressed in discrete neuroendocrine and stress-related nuclei of the rodent CNS. To determine the physiological role of urocortin 2, mice null for urocortin 2 were generated and HPA axis activity, ingestive, and stress-related behaviors and alterations in expression levels of CRF-related ligands and receptors were examined. Here we report that female, but not male, mice lacking urocortin 2 exhibit a significant increase in the basal daily rhythms of ACTH and corticosterone and a significant decrease in fluid intake and depressive-like behavior. The differential phenotype of urocortin 2 deficiency in female and male mice may imply a role for urocortin 2 in these gender differences.
Chen
Alon
A
Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, California 92037, USA.
Zorrilla
Eric
E
Smith
Sean
S
Rousso
David
D
Levy
Coree
C
Vaughan
Joan
J
Donaldson
Cindy
C
Roberts
Amanda
A
Lee
Kuo-Fen
KF
Vale
Wylie
W
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D002478:Cells, Cultured; D002678:Chimera; D002940:Circadian Rhythm / Q000235:genetics*; D003345:Corticosterone / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000235:genetics* / Q000378:metabolism; D003866:Depressive Disorder / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D004326:Drinking / Q000502:physiology; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism* / Q000503:physiopathology; D008024:Ligands; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D010913:Pituitary-Adrenal System / Q000378:metabolism* / Q000503:physiopathology; D012727:Sex Characteristics; D013315:Stress, Psychological / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D054832:Urocortins
D008024:Ligands; D054832:Urocortins; C518358:urocortin 2, mouse; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone