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Differential Expression of a Cutaneous Corticotropin-Releasing Hormone System

Department of Pathology (A.S., A.P.), University of Tennessee Health Science Center, Memphis, Tennessee 38163; Department of Biomedical Sciences (D.J.T.), University of Bradford, West Yorkshire BD7 1DP, United Kingdom; Center for Neuropharmacology and Neuroscience (J.E.M.), Albany Medical College, Albany, New York 12208; and Department of Internal Medicine (J.W.), Southern Illinois University, Springfield, Illinois 62794

Address all correspondence and requests for reprints to: Andrzej T. Slominski, M.D., Ph.D., Department of Pathology and Laboratory Medicine, 930 Madison Avenue, 5th Floor, Memphis, Tennessee 38163. E-mail: aslominski{at}utmem.edu.

We completed the mapping of a cutaneous CRH signaling system in two species with widely different determinants of skin functions, humans and mice. In human skin, the CRH receptor (CRH-R) 1 was expressed in all major cellular populations of epidermis, dermis, and subcutis with CRH-R1 being the most prevalent isoform. The CRH-R2 gene was expressed solely in hair follicle keratinocytes and papilla fibroblasts, whereas CRH-R2 antigen was localized predominantly in hair follicles, sebaceous and eccrine glands, muscle and blood vessels. In mouse skin, the CRH-R2 gene and protein were widely expressed in all cutaneous compartments and in cultured normal and malignant melanocytes. CRH-binding protein mRNA was present in dermal fibroblasts, melanoma cells, and sc fat of human skin and undetectable in mouse skin. The urocortin II gene was expressed equally in mouse and human skin. Taken together with our previous investigations, the present studies document the preferential expression of CRH-R1 in human skin, which mirrors CRH-R2 expression patterns in human and mouse skin. They are likely reflecting different functional activities of human and mouse skin. The adnexal location of CRH-R2 suggests a role for the receptor in hair growth. The differential interspecies CRH signaling expression pattern probably reflects adaptation to species-specific skin function determinants.

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