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This version published online on January 21, 2004
Endocrinology, doi:10.1210/en.2003-1570
A more recent version of this article appeared on May 1, 2004
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Submitted on November 19, 2003
Accepted on January 14, 2004

Urocortin II gene is highly expressed in mouse skin and skeletal muscle tissues: localization, basal expression in CRFR1 and CRFR2-null mice and regulation by glucocorticoids

Alon Chen, Amy Blount, Joan Vaughan, Bhawanjit Brar, and Wylie Vale*

Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, La Jolla, California 92037, USA

* To whom correspondence should be addressed. E-mail: vale{at}salk.edu.

Peptides encoded by the Urocortin II (Ucn II) gene, also known as stresscopin-related peptide were recently identified as new members of the CRF family. Ucn II is a specific ligand for the type 2 CRF receptor. We have demonstrated the peripheral distribution of mouse Ucn II transcripts by using specific mUcn II RNase protection assays, RT-PCR, Southern hybridization and DNA sequencing. While Ucn II mRNA is widely expressed in a variety of peripheral tissues, we found it to be most highly expressed in the skin and skeletal muscle tissues. Using a specific RIA for mUcn II we detected Ucn II-like immunoreactivity (ir) in acid extracts of mouse brain, muscle and skin. Immunohistochemical studies revealed Ucn II-like ir in both skin epidermis and adnexal structures and in the skeletal muscle myocytes. Ucn II mRNA and ir were also observed in neonatal skeletal muscle cultures where Ucn II was localized to the myotube. We found a significant increase in Ucn II mRNA levels in the skin, but not skeletal muscle, of both CRFR1 and CRFR2-null mice compared with their wild-type littermates. We show that administration of dexamethasone to mice results in a decrease of Ucn II mRNA levels in the back skin region 12 h following intraperitoneal injections. Removal of the adrenal gland significantly increases the levels of Ucn II mRNA in the skin, which were reduced back to normal levels following corticosterone replacement. Further examining the distribution and regulation of CRFR2 and its specific ligand Ucn II in the skin and skeletal muscle tissues may reveal the manner by which the CRFR2 pathway is involved in the physiological responses to stress in these tissues and in other pathopysiologies of the skin and muscle.
Key words: Urocortin II • skin • skeletal muscle • corticotropin releasing factor (CRF) • CRF receptors • glucocorticoids




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