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Agouti-signaling protein precursor (ASP) (Agouti switch protein) [AGTI] [AGTIL] [ASP]


Efficacy of an agonist of α-MSH, the palmitoyl tetrapeptide-20, in hair pigmentation.

Hair greying (i.e., canities) is a component of chronological ageing and occurs regardless of gender or ethnicity. Canities is directly linked to the loss of melanin and increase in oxidative stress in the hair follicle and shaft. To promote hair pigmentation and reduce the hair greying process, an agonist of α-melanocyte-stimulating hormone (α-MSH), a biomimetic peptide (palmitoyl tetrapeptide-20; PTP20) was developed. The aim of this study was to describe the effects of the designed peptide on hair greying. Effect of the PTP20 on the enzymatic activity of catalase and the production of H O by Human Follicle Dermal Papilla Cells (HFDPC) was evaluated. Influence of PTP20 on the expression of melanocortin receptor-1 (MC1-R) and the production of melanin were investigated. Enzymatic activity of sirtuin 1 (SIRT1) after treatment with PTP20 was also determined. Ex vivo studies using human micro-dissected hairs allowed to visualize the effect of PTP20 on the expression in hair follicle of catalase, TRP-1, TRP-2, Melan-A, ASIP, and MC1-R. These investigations were completed by a clinical study on 15 human male volunteers suffering from premature canities. The in vitro and ex vivo studies revealed the capacity of the examined PTP20 peptide to enhance the expression of catalase and to decrease (30%) the intracellular level of H O . Moreover, PTP20 was shown to activate in vitro and ex vivo the melanogenesis process. In fact, an increase in the production of melanin was shown to be correlated with elevated expression of MC1-R, TRP-1, and Melan-A, and with the reduction in ASIP expression. A modulation on TRP-2 was also observed. The pivotal role of MC1-R was confirmed on protein expression analysed on volunteer's plucked hairs after 3 months of the daily application of lotion containing 10 ppm of PTP20 peptide. The current findings demonstrate the ability of the biomimetic PTP20 peptide to preserve the function of follicular melanocytes. The present results suggest potential cosmetic application of this newly designed agonist of α-MSH to promote hair pigmentation and thus, reduce the hair greying process.

MeSH Terms

  • Adolescent
  • Adult
  • Aged
  • Aging
  • Catalase
  • Cells, Cultured
  • Female
  • HEK293 Cells
  • Hair Color
  • Hair Follicle
  • Humans
  • Male
  • Oligopeptides
  • Receptor, Melanocortin, Type 1
  • Sirtuin 1
  • Transcriptional Activation
  • Young Adult
  • alpha-MSH


  • canities
  • clinical assay
  • hair treatment
  • peptide
  • α-MSH/MC1-R

A polymorphism in the agouti signaling protein gene is associated with human pigmentation.

In mice and humans, binding of alpha-melanocyte--stimulating hormone to the melanocyte-stimulating--hormone receptor (MSHR), the protein product of melanocortin-1 receptor (MC1R) gene, leads to the synthesis of eumelanin. In the mouse, ligation of MSHR by agouti signaling protein (ASP) results in the production of pheomelanin. The role of ASP in humans is unclear. We sought to characterize the agouti signaling protein gene (ASIP) in a group of white subjects, to assess whether ASIP was a determinant of human pigmentation and whether this gene may be associated with increased melanoma risk. We found no evidence of coding-region sequence variation in ASIP, but detected a g.8818A-->G polymorphism in the 3' untranslated region. We genotyped 746 participants in a study of melanoma susceptibility for g.8818A-->G, by means of polymerase chain reaction and restriction fragment--length polymorphism analysis. Among the 147 healthy controls, the frequency of the G allele was.12. Carriage of the G allele was significantly associated with dark hair (odds ratio 1.8; 95% confidence interval [CI] 1.2--2.8) and brown eyes (odds ratio 1.9; 95% CI 1.3--2.8) after adjusting for age, gender, and disease status. ASIP g.8818A-->G was not associated independently with disease status. This is the first report of an association of ASIP with specific human pigmentation characteristics. It remains to be investigated whether the interaction of MC1R and ASIP can enhance prediction of human pigmentation and melanoma risk.

MeSH Terms

  • Aging
  • Agouti Signaling Protein
  • European Continental Ancestry Group
  • Eye Color
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Hair Color
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Male
  • Melanoma
  • Odds Ratio
  • Phenotype
  • Pigmentation
  • Polymorphism, Genetic
  • Proteins
  • Sex Characteristics
  • Skin Pigmentation