Corticotropin releasing hormone and related peptides can act as bioregulatory factors in human keratinocytes.
Following previous findings in human skin of the functional expression of genes for the corticotropin releasing hormone (CRH) receptor type 1 (CRH-R1) and CRH itself, we searched for local phenotypic effects for peptides related to CRH. We now report that CRH, sauvagine, and urocortin inhibit proliferation of human HaCaT keratinocytes in a dose-dependent manner. The peptides produced variable cyclic adenosine 3':5'-monophosphate stimulation, with CRH having the highest potency. Binding of iodine 125 CRH to intact keratinocytes was inhibited by increasing doses of CRH, sauvagine, or urocortin, all showing equal inhibitory potency. Immunocytochemistry identified CRH-R1 immunoreactivity in HaCaT keratinocytes. In conclusion, CRH (exogenous or produced locally) and the related urocortin and sauvagine peptides can modify human keratinocyte phenotype through a receptor-mediated pathway.
Slominski
A T
AT
Department of Pathology, Medical Center, Loyola University, Maywood, Illinois 60153, USA. aslomin@wpo.it.luc.edu
Roloff
B
B
Zbytek
B
B
Wei
E T
ET
Fechner
K
K
Curry
J
J
Wortsman
J
J
D029845:Amphibian Proteins; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism* / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D036361:Peptide Hormones; D010455:Peptides / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism; D054832:Urocortins; D000099052:CRF Receptor, Type 1
D029845:Amphibian Proteins; D036361:Peptide Hormones; D010455:Peptides; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; D000099052:CRF Receptor, Type 1; C025727:sauvagine; D003346:Corticotropin-Releasing Hormone; D000242:Cyclic AMP