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Urocortin II Gene Is Highly Expressed in Mouse Skin and Skeletal Muscle Tissues: Localization, Basal Expression in Corticotropin-Releasing Factor Receptor (CRFR) 1- and CRFR2-Null Mice, and Regulation by Glucocorticoids

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

Address all correspondence and requests for reprints to: Wylie Vale, Ph.D, Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037. E-mail: vale{at}salk.edu.

Peptides encoded by the Urocortin (Ucn) II gene, also known as stresscopin-related peptide, were recently identified as new members of the corticotropin-releasing factor (CRF) family. Ucn II is a specific ligand for the type 2 CRF receptor (CRFR). We have demonstrated the peripheral distribution of mouse Ucn (mUcn) II transcripts by using specific mUcn II ribonuclease protection assays, RT-PCR, Southern hybridization, and DNA sequencing. Although 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 in which Ucn II was localized to the myotube. We found a significant increase in Ucn II mRNA levels in the skin, but not in skeletal muscle, of both CRFR1- and CRFR2-null mice compared with their wild-type littermates. We showed that administration of dexamethasone to mice resulted in a decrease of Ucn II mRNA levels in the back skin region 12 h after ip injections. Removal of the adrenal gland significantly increased the levels of Ucn II mRNA in the skin, and the levels were reduced back to normal levels after corticosterone replacement. Further examination of 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 pathophysiologies of the skin and muscle.

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