title: Corticotropin-releasing hormone skin signaling is receptor-mediated and is predominant in the sebaceous glands.
abstract: There is increasing evidence that the sebaceous gland expresses receptors for several neuropeptides and is involved in responses to stress. Among them, corticotropin-releasing hormone (CRH) was currently found to be produced also in the skin. In this study, the distribution of CRH, CRH receptors 1 and 2 (CRH-R1 and CRH-R2), and CRH binding protein (CRH-BP) in cultured human (SZ95) sebocytes was further characterized. Moreover, the effects of CRH and CRH-like peptides on proliferation and inflammatory signaling of CRH receptor-expressing SZ95 sebocytes IN VITRO were investigated. Urocortin (Uct), urotensin and sauvagine are recently described members of the family of structurally related CRH-like peptides, whereas Uct shares a 45% homology with CRH. CRH and Uct inhibited SZ95 sebocyte proliferation with CRH also stimulating interleukin-6 (IL-6) and interleukin-8 (IL-8) release from SZ95 sebocytes. However, CRH had no effect on interleukin-1alpha and interleukin-1beta production in these cells. alpha-Helical-CRF, a CRH antagonistic peptide, annulled the CRH effect on SZ95 sebocyte proliferation and interleukin secretion, while the non-peptidic CRH-R1 selective antagonist antalarmin inhibited the increased production of neutral lipids caused by CRH. In conclusion, CRH, and to a lesser extent Uct, may be involved in signaling of stress pathophysiology in the skin. However, further investigations into the downstream effects of CRH and Uct are required to elucidate the mechanism by which these neuropeptides could establish a stress-related pathophysiological condition in the skin.
authors.affiliation: Department of Dermatology, Charité Universitaetsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Krause
authors.forename: A
authors.initials: A
authors.lastname: Schnitger
authors.forename: S
authors.initials: S
authors.lastname: Fimmel
authors.forename: E
authors.initials: E
authors.lastname: Glass
authors.forename: C C
authors.initials: CC
authors.lastname: Zouboulis
mesh_terms: D029845:Amphibian Proteins; D002352:Carrier Proteins / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D036361:Peptide Hormones; D010455:Peptides / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism / Q000502:physiology*; D012627:Sebaceous Glands / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism*; D012879:Skin Physiological Phenomena; D054832:Urocortins; D014579:Urotensins / Q000494:pharmacology
chemical_list: D029845:Amphibian Proteins; D002352:Carrier Proteins; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D036361:Peptide Hormones; D010455:Peptides; D011743:Pyrimidines; D011758:Pyrroles; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; D014579:Urotensins; C069206:alpha helical corticotropin-releasing hormone; C103016:antalarmin; C067133:corticotropin releasing factor-binding protein; C025727:sauvagine; D003346:Corticotropin-Releasing Hormone