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This Article Full Text Full Text (PDF) All Versions of this Article: 293/1/E259    most recent 00616.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Zalutskaya, A. A. Articles by Abou-Samra, A. B. Search for Related Content PubMed PubMed Citation Articles by Zalutskaya, A. A. Articles by Abou-Samra, A. B.

Impaired adaptation to repeated restraint and decreased response to cold in urocortin 1 knockout mice

¹Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; and ²Wayne State University School of Medicine, Detroit, Michigan

Submitted 16 November 2006 ; accepted in final form 29 March 2007

Urocortin 1 (UCN1) is a corticotropin-releasing factor (CRF)-like peptide whose role in stress is not well characterized. To study the physiological role of UCN1 in the response of the hypothalamic-pituitary-adrenal (HPA) axis to stress, we generated UCN1-knockout (KO) mice and examined their adaptation to repeated restraint and to cold environment. Wild-type (WT) and UCN1-KO animals were restrained hourly for 15 min from 9 AM to 2 PM, and blood samples were obtained for corticosterone measurement. WT animals adapted to repeated restraint with a decreased corticosterone response; the restraint-stimulated corticosterone levels fell from 215 ± 31 ng/ml in naïve animals to 142 ± 50 ng/ml in mice subjected to repeated restraint (P < 0.01) and from 552 ± 98 to 314 ± 58 ng/ml (P < 0.001) in males and females, respectively. Male UCN1-KO mice did not show any adaptation to repeated restraint; instead, restraint-stimulated corticosterone levels were increased from 274 ± 80 ng/ml in naïve animals to 480 ± 75 ng/ml in mice subjected to repeated restraint (P < 0.001). Female UCN1-KO mice showed only a partial adaptation to repeated restraint, with a decrease in the restraint-stimulated corticosterone response from 631 ± 102 ng/ml in naïve animals to 467 ± 78 ng/ml in mice subjected to repeated restraint (P < 0.01). In addition, UCN1-KO mice showed no corticosterone response to 2-h cold environment. These data demonstrate an important role for UCN1 in the HPA axis adaptation to repeated restraint and in the corticosterone response to a cold environment.

corticosterone; stress; mice