Impaired adaptation to repeated restraint and decreased response to cold in urocortin 1 knockout mice.
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.
Zalutskaya
Alena A
AA
Endocrine Unit, Massachusetts General Hospital, Thier 1051, 55 Fruit St., Boston, MA 02114, USA. azalutskaya@partners.org
Arai
Maya
M
Bounoutas
George S
GS
Abou-Samra
Abdul B
AB
D000222:Adaptation, Physiological / Q000235:genetics*; D000818:Animals; D003080:Cold Temperature; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000235:genetics*; D005260:Female; D007103:Immobilization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012149:Restraint, Physical; D012727:Sex Characteristics; D013315:Stress, Psychological / Q000097:blood / Q000235:genetics; D054832:Urocortins
D054832:Urocortins; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone