Corticotropin releasing hormone and the skin.
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.
Slominski
Andrzej
A
Department of Pathology, University of Tennessee Health Science Center, Memphis, TN 38163, USA. aslominski@utmem.edu
Zbytek
Blazej
B
Zmijewski
Michal
M
Slominski
Radomir M
RM
Kauser
Sobia
S
Wortsman
Jacobo
J
Tobin
Desmond J
DJ
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
D010455:Peptides; D020033:Protein Isoforms; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone