title: Differential expression of HPA axis homolog in the skin.
abstract: Human skin expresses elements of the hypothalamo-pituitary-adrenal (HPA) axis including pro-opiomelanocortin (POMC), corticotropin releasing hormone (CRH), the CRH receptor-1 (CRH-R1), key enzymes of corticosteroid synthesis and synthesizes glucocorticoids. Expression of these elements is organized in functional, cell type-specific regulatory loops, which imitate the signaling hierarchy of the HPA axis. In melanocytes and fibroblasts CRH-induced CRH-R1 stimulation upregulates POMC expression and production of ACTH through activation of cAMP dependent pathway(s). Melanocytes respond with enhanced production of cortisol and corticosterone, which is dependent on POMC activity. Fibroblasts respond to CRH and ACTH with enhanced production of corticosterone, but not cortisol, which is produced constitutively. Organ-cultured human scalp hair follicles also show a fully functional HPA axis equivalent, including cortisol synthesis and secretion and negative feedback regulation by cortisol on CRH expression. Thus, differential, CRH-driven responses of defined cutaneous cell populations reproduce key features of the central HPA axis at the tissue/single cell levels.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Tennessee, HSC, Memphis, TN 38163, USA. aslominski@utmem.edu
authors.forename: Andrzej
authors.initials: A
authors.lastname: Slominski
authors.forename: Jacobo
authors.initials: J
authors.lastname: Wortsman
authors.forename: Robert C
authors.initials: RC
authors.lastname: Tuckey
authors.forename: Ralf
authors.initials: R
authors.lastname: Paus
mesh_terms: D000818:Animals; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D008544:Melanocytes / Q000502:physiology; D010913:Pituitary-Adrenal System / Q000502:physiology*; D012879:Skin Physiological Phenomena; D013256:Steroids / Q000096:biosynthesis
chemical_list: D013256:Steroids