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 g enes for the corticotropin releasing hormone (CRH) receptor type 1 (CRH-R1) and CRH itself, we searched for local phenotypic effects for peptides rela ted to CRH. We now report that CRH, sauvagine, and urocortin inhibit prolif eration of human HaCaT keratinocytes in a dose-dependent manner. The peptid es produced variable cyclic adenosine 3':5'-monophosphate stimulation, with CRH having the highest potency. Binding of iodine 125 CRH to intact kerati nocytes 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 modi fy human keratinocyte phenotype through a receptor-mediated pathway.