Differential Expression of a Cutaneous Corticotropin-Releasing Hormone System

• Published in: Endocrinology (Philadelphia) Vol. 145; no. 2; pp. 941 - 950
• Main Authors: Slominski, Andrzej, Pisarchik, Alexander, Tobin, Desmond J, Mazurkiewicz, Joseph E, Wortsman, Jacobo
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.02.2004
• Subjects: Alternative Splicing; Animals; Biological and medical sciences; Carrier Proteins - genetics; Cells, Cultured; Corticotropin-Releasing Hormone - physiology; Dermis - chemistry; Epidermis - chemistry; Female; Fibroblasts - chemistry; Fundamental and applied biological sciences. Psychology; Gene Expression; Hair Follicle - chemistry; Humans; Immunohistochemistry; Keratinocytes - chemistry; Melanocytes - chemistry; Mice; Mice, Inbred C57BL; Organ Specificity; Protein Isoforms - analysis; Protein Isoforms - genetics; Receptors, Corticotropin-Releasing Hormone - analysis; Receptors, Corticotropin-Releasing Hormone - genetics; Reverse Transcriptase Polymerase Chain Reaction; Scalp; Signal Transduction; Skin - chemistry; Species Specificity; Urocortins; Vertebrates: endocrinology; Hypothalamic hormone; Skin; Hormone releasing factor; Corticotropin releasing factor
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2003-0851

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-R1α 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.