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Binding of melanotropic hormones to the melanocortin receptor MC1R on human melanocytes stimulates proliferation and melanogenesis.

Authors
Suzuki, I; Cone, RD; Im, S; Nordlund, J; Abdel-Malek, ZA
Citation
Endocrinology, 137(5):1627-1633, 1996
Journal Title
Endocrinology
ISSN
0013-72271945-7170
Abstract
alpha-Melanocyte stimulating hormone (alpha-MSH) and ACTH increase the proliferation and melanogenesis of cultured human melanocytes. To further analyze how melanotropins produce these biological effects, we investigated the regulation of the melanocortin receptor MC1R expression by alpha-MSH and ACTH using Northern blot analysis and determine the relative affinity of the receptor for the structurally similar peptides alpha-MSH, ACTH, beta-MSH, and gamma-MSH. We also determined the relative potencies of these hormones to stimulate cAMP formation, tyrosinase activity, and melanocyte proliferation. The order of affinity and potency of the noted melanotropins in these assays were alpha-MSH = ACTH > beta-MSH > gamma-MSH. Because the binding affinity of each of these melanotropins for the MC1R correlated with its ability to stimulate human melanocyte proliferation and melanogenesis, we conclude that these effects are mediated specifically by binding to and activation of the MC1R. gamma-MSH stimulated cAMP formation without affecting proliferation or melanogenesis. However, we found that relative to alpha-MSH, the effect of gamma-MSH on cAMP formation was transient. Our results suggest that alpha-MSH, ACTH, and possibly beta-MSH, but not gamma-MSH, are capable of a physiological role in regulating human pigmentation, and that melanocytes in human skin are a specific target for these hormones.
MeSH terms
Adrenocorticotropic Hormone/pharmacologyAmino Acid SequenceBlotting, NorthernCell Division/*drug effectsCells, CulturedCyclic AMP/biosynthesisDose-Response Relationship, DrugHumansMaleMelanins/*biosynthesisMelanocyte-Stimulating Hormones/*metabolism/pharmacologyMelanocytes/*metabolismMolecular Sequence DataMonophenol Monooxygenase/metabolismReceptors, Corticotropin/*metabolismReceptors, Melanocortinalpha-MSH/metabolism/pharmacology
DOI
10.1210/endo.137.5.8612494
PMID
8612494
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Dermatology
AJOU Authors
임, 성빈
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