title: Corticotropin releasing hormone and the skin.
abstract: Cotricotropin-releasing hormone (CRH) and related peptides are produced in skin that is dependent on species and anatomical location. Local peptide production is regulated by ultraviolet radiation (UVR), glucocorticoids and phase of the hair cycle. The skin also expresses the corresponding receptors (CRH-R1 and CRH-R2), with CRH-R1 being the major receptor in humans. CRH-R1 is expressed in epidermal and dermal compartments, and CRH-R2 predominantly in dermal structures. The gene coding for CRH-R1 generates multiple isoforms through a process modulated by UVR, cyclic adenosine monophosphate (cAMP) and phorbol 12-myristate 13-acetate. The phenotypic effects of CRH in human skin cells are largely mediated by CRH-R1alpha through increases in concentrations of cAMP, inositol triphosphate (IP3), or Ca2+ with subsequent activation of protein kinases A (PKA) and C (PKC) dependent pathways. CRH also modulates the activity of nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-kappaB), activator protein 1 (AP-1) and cAMP responsive element binding protein (CREB). The cellular functions affected by CRH depend on cell type and nutritional status and include modulation of differentiation program(s), proliferation, viability and immune activity. The accumulated evidence indicates that cutaneous CRH is also a component of a local structure organized similarly to the hypothalamo-pituitary-adrenal axis.
authors.affiliation: Department of Pathology, University of Tennessee Health Science Center, Memphis, TN 38163, USA. aslominski@utmem.edu
authors.forename: Andrzej
authors.initials: A
authors.lastname: Slominski
authors.forename: Blazej
authors.initials: B
authors.lastname: Zbytek
authors.forename: Michal
authors.initials: M
authors.lastname: Zmijewski
authors.forename: Radomir M
authors.initials: RM
authors.lastname: Slominski
authors.forename: Sobia
authors.initials: S
authors.lastname: Kauser
authors.forename: Jacobo
authors.initials: J
authors.lastname: Wortsman
authors.forename: Desmond J
authors.initials: DJ
authors.lastname: Tobin
mesh_terms: D017398:Alternative Splicing; D018929:Cell Culture Techniques; D003346:Corticotropin-Releasing Hormone / Q000502:physiology*; D018859:Hair Follicle / Q000378:metabolism; D006801:Humans; D007030:Hypothalamo-Hypophyseal System; D010455:Peptides; D010641:Phenotype; D010913:Pituitary-Adrenal System; D020033:Protein Isoforms; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics* / Q000378:metabolism*; D015290:Second Messenger Systems; D015398:Signal Transduction; D012867:Skin / Q000166:cytology; D012879:Skin Physiological Phenomena; D012880:Skin Pigmentation; D014466:Ultraviolet Rays; D054832:Urocortins; D000099052:CRF Receptor, Type 1
chemical_list: D010455:Peptides; D020033:Protein Isoforms; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone