Effects of a Superpotent Melanotropic Peptide in Combination With Solar UV Radiation on Tanning of the Skin in Human Volunteers | Dermatology | JAMA Dermatology | JAMA Network
[Skip to Navigation]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address Please contact the publisher to request reinstatement.
Hadley  MEBrake  Ded The melanotropic hormones  Endocrinology. 4th ed New York, NY Simon & Schuster1982;153- 176Google Scholar
Thody  AJHiggins  EMWakamatsu  KIto  SBurchill  SAMarks  JM Pheomelanin as well as eumelanin is present in human epidermis  J Invest Dermatol. 1991;97340- 344PubMedGoogle ScholarCrossref
Fitzpatrick  TB The validity and practicality of sun-reactive skin types I through VI  Arch Dermatol. 1988;124869- 871PubMedGoogle ScholarCrossref
Valverde  PHealy  EJackson  IRees  JLThody  AJ Variants of the melanocyte-stimulating hormone receptor gene are associated with red hair and fair skin in humans  Nat Genet. 1995;11328- 330PubMedGoogle ScholarCrossref
Box  NFDuffy  DLIrving  RE  et al.  Melanocortin-1 receptor genotype is a risk factor for basal and squamous cell carcinoma  J Invest Dermatol. 2001;116224- 229PubMedGoogle ScholarCrossref
Palmer  JSDuffy  DLBox  NF  et al.  Melanocortin-1 receptor polymorphisms and risk of melanoma: is the association explained solely by pigmentation phenotype?  Am J Hum Genet. 2000;66176- 186PubMedGoogle ScholarCrossref
Sawyer  TKSanfilippo  VJHruby  VJ  et al.  4-Norleucine, 7-D-phenylalanine-alpha-melanocyte-stimulating hormone: a highly potent alpha-melanotropin with ultralong biological activity  Proc Natl Acad Sci U S A. 1980;775754- 5758PubMedGoogle ScholarCrossref
Levine  NSheftel  SNEytan  T  et al.  Induction of skin tanning by subcutaneous administration of a potent synthetic melanotropin  JAMA. 1991;2662730- 2736PubMedGoogle ScholarCrossref
Dorr  RTDvorakova  KBrooks  C  et al.  Increased eumelanin expression and tanning is induced by a superpotent melanotropin [Nle4-D-Phe7]-α-MSH in humans  Photochem Photobiol. 2000;72526- 532PubMedGoogle ScholarCrossref
Lipton  JMCeriani  GMacaluso  A  et al.  Antiinflammatory effects of the neuropeptide alpha-MSH in acute, chronic and systemic inflammation  Ann N Y Acad Sci. 1994;741137- 148PubMedGoogle ScholarCrossref
Ceriani  GDiaz  JMurphree  SCatania  ALipton  JM The neuropeptide alpha-melanocyte-stimulating hormone inhibits experimental arthritis in rats  Neuroimmunomodulation. 1994;128- 132PubMedGoogle ScholarCrossref
Chiao  HFoster  RThomas  JLipton  JStar  RA Alpha-melanocyte-stimulating hormone reduces endotoxin-induced liverinflammation  J Clin Invest. 1996;972038- 2044PubMedGoogle ScholarCrossref
Levine  NDorr  RTErtl  GABrooks  CAlberts  DS Effects of a potent synthetic melanotropin, Nle4-D-Phe7-a-MSH (melanotan-1) on tanning: a dose-ranging study  J Dermatolog Treat. 1999;10127- 132Google ScholarCrossref
Sullivan Jr  JDValois  FWWatson  SWBernheimer  AWed. Endotoxins: the Limulus amebocyte lysate system  Mechanisms of Bacterial Toxicology. New York, NY John Wiley & Sons Inc1976;217- 220Google Scholar
Porgess  SBKaidbey  KHGrove  GL Quantification of visible light-induced melanogenesis in human skin  Photodermatol. 1988;5197- 200PubMedGoogle Scholar
Westerhof  Wvan Hasselt  BAAMKammeijer  A Quanitification of UV-induced erythema with a portable computer controlled chromometer  Photodermatol. 1986;3310- 314PubMedGoogle Scholar
Seitz  JCWhitmore  CG Measurements of erythematous and tanning responses in human skin using a tri-stimulus colorimeter  Dermatologica. 1988;17770- 75PubMedGoogle ScholarCrossref
Gilchrest  BASoter  NAStoff  JSMihm Jr  MC The human sunburn reaction: histologic and biochemical studies  J Am Acad Dermatol. 1981;5411- 422PubMedGoogle ScholarCrossref
Cesarini  JPChardon  ABinet  OHourseau  CGrollier  JF High-protection sunscreen formulation prevents UVB-induced sunburn cell formation  Photodermatol. 1989;620- 23PubMedGoogle Scholar
Picker  LJMichie  RARott  LSButcher  EC A unique phenotype of skin associated lymphocytes in humans: preferential expression of the HECA-452 epitope by benign and malignant T cells at cutaneoussites  Am J Pathol. 1990;1361053- 1068PubMedGoogle Scholar
Szabo  G The number of melanocytes in human epidermis  BMJ. 1954;11016- 1017Google ScholarCrossref
Karagas  MRStannard  VAMott  LASlattery  MJSpencer  SKWeinstock  MA Use of tanning devices and risk of basal cell and squamous cell skin cancers  J Natl Cancer Inst. 2002;94224- 226PubMedGoogle ScholarCrossref
Mason  MJVan Epps  D Modulation of IL-1, tumor necrosis factor, and C5a-mediated murine neutrophil migration by alpha-melanocyte-stimulating hormone  J Immunol. 1989;1421646- 1651PubMedGoogle Scholar
Rheins  LACotleur  ALKleier  RSHoppenjans  WBSaunder  DNNordhund  JJ Alpha-melanocyte stimulating hormone modulates contact hypersensitivity responsiveness in C57/BL6 mice  J Invest Dermatol. 1989;93511- 517PubMedGoogle ScholarCrossref
Mountjoy  KGRibbins  LSMortrud  MTCone  RC The cloning of a family of genes that encode the melanocortin receptors  Science. 1992;2571248- 1251PubMedGoogle ScholarCrossref
Romero-Gaillet  CAberdam  EClement  MOrtonne  J-PBallotti  R Nitric oxide produced by ultraviolet-irradiated keratinocytes stimulates melanogenesis  J Clin Invest. 1997;99635- 642PubMedGoogle ScholarCrossref
Tsatmali  MGraham  ASzatkowski  D  et al.  Alpha-melanocyte-stimulating hormone modulates nitric oxide production in melanocytes  J Invest Dermatol. 2000;114520- 526PubMedGoogle ScholarCrossref
Mountjoy  KGMortrud  MTLow  MJSimerly  RBCone  RD Localization of the melanocortin-4 receptor (MC4-R) in neuroendocrine and autonomic control circuits in the brain  Mol Endocrinol. 1994;81298- 1308PubMedGoogle Scholar
Yang  Y-KDickinson  CHaskell-Luevano  CGantz  I Molecular basis for the interaction of [Nle4-D-Phe7]-melanocyte stimulating hormone with the human melanocortin-1 receptor(melanocyte a-MSH receptor)  J Biol Chem. 1997;27223000- 23010PubMedGoogle ScholarCrossref
Bhardwaj  RHadley  MEDorr  RTDvorakova  KBrooks  CBlanchard  J Pharmacologic response of a controlled release PLGA formulation for the alpha-melanocyte stimulating hormone analog, melanotan-I  Pharm Res. 2000;17593- 599PubMedGoogle ScholarCrossref
July 2004

Effects of a Superpotent Melanotropic Peptide in Combination With Solar UV Radiation on Tanning of the Skin in Human Volunteers

Author Affiliations

From the Department of Medicine, Cancer Center Division (Drs Dorr, Powell, and Alberts, and Ms Brooks), and Dermatology Section (Drs Ertl, Levine,and Bangert), University of Arizona, Tucson; Department of Radiation Oncology, Stanford University, Stanford, Calif (Dr Powell); and EpiTan Ltd, Melbourne,Australia (Dr Humphrey). Dr Ertl in now with Palm Canyon Dermatology, Yuma, Ariz. Dr Dorr is a consultant to EpiTan Ltd, and Drs Alberts, Dorr, and Levineare shareholders in EpiTan Ltd.

Arch Dermatol. 2004;140(7):827-835. doi:10.1001/archderm.140.7.827

Objective  Three phase 1 clinical trials of a superpotent melanotropic peptide, melanotan-1 (MT-1, or [Nle4-D-Phe7]α-melanocyte-stimulatinghormone) were performed to demonstrate safety for MT-1 therapy combined with UV-B light or sunlight.

Design  Open-label studies at 2 dose levels of MT-1 combined with small doses of UV-B to the neck or buttock or full sunlight to half of the back.

Setting  Dermatology clinics at the Arizona Health Sciences Center, Tucson.

Interventions  The first study randomized 4 subjects to MT-1 (0.08 mg/kg per day subcutaneously) and 4 subjects to injections of isotonic sodium chloride (9%) solution for10 days, followed by neck irradiation with 3 times the minimal erythema dose (MED) of UV-B light. In the next study (n = 12), the MT-1 dosage was increasedto 0.16 mg/kg per day for 10 days, with UV-B radiation (0.25-0.75 MED) given to a buttock site for 5 days during (n = 7) or after (n = 5) MT-1 administration.A final study randomized 8 subjects to 3 to 5 days of sunlight to half ofthe back or to sunlight plus 0.16 mg/kg of MT-1 for 5 days per week for 4weeks.

Results  Tanning in the first study was achieved in 3 of 4 subjects receiving MT-1, and these subjects also had 47% fewer sunburn cells at the irradiated neck site. More skin sites darkened with the higher dose of MT-1 in the second study. In the third study, there was significantly enhanced tanning of theback in the MT-1 group, and this was maintained at least 3 weeks longer than the tanning in the sunlight-only controls, who required 50% more sun-exposuretime for equivalent tanning.

Main Outcome Measure  There were no pathologic findings at any UV-B or sun-exposed sites in any subject. Toxic effects due to MT-1 were minor, consisting of nausea andtransient facial flushing.

Conclusion  Melanotan-1 can be safely combined with UV-B light or sunlight and appears to act synergistically in the tanning response to light.