The PI3K pathway induced by αMSH exerts a negative feedback on melanogenesis and contributes to the release of pigment

Pigment Cell Melanoma Res. 2021 Jan;34(1):72-88. doi: 10.1111/pcmr.12910. Epub 2020 Jul 16.


The melanocortin-1 receptor (MC1R) belongs to the family of the G protein-coupled receptor (GPCR). Activated GPCRs can promote the phosphoinositide 3-kinase (PI3K) pathway. Few studies deal with the role of the PI3K pathway activation in response to αMSH. On B16-F10 cell line, we investigated the αMSH-dependent modulation of pAKT/AKT, as a key element of the PI3K pathway after rapid and prolonged stimulation. We demonstrated that αMSH triggers a rapid modulation of AKT which culminates in an increase in its phosphorylation. We highlighted a comparable upregulation of pAKT after exposure to αMSH on primary cultures of normal human melanocytes (NHMs) expressing a wild-type MC1R. On B16-F10 cells, NHMs, and an ex vivo model of human skin biopsies, we explored the influence of PI3K/AKT signaling triggered by αMSH, focusing on the control of melanogenesis and pigment release. We showed that the αMSH-dependent PI3K/AKT pathway exerts a negative feedback on melanogenesis and promotes the extracellular release of pigment. We strengthened the role of the PI3K/AKT pathway triggered by αMSH in preserving redox equilibrium and genome integrity, highlighting its role in affecting cell survival.

Keywords: AKT; B16-F10; PI3K; apoptosis; melanin; melanocytes; melanogenesis; pAKT; αMSH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Feedback, Physiological*
  • Humans
  • Melanins / metabolism*
  • Melanocytes / cytology*
  • Melanocytes / drug effects
  • Melanocytes / metabolism
  • Melanoma, Experimental / metabolism
  • Melanoma, Experimental / pathology*
  • Mice
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphorylation
  • Pigmentation
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • alpha-MSH / pharmacology*


  • Melanins
  • alpha-MSH
  • Proto-Oncogene Proteins c-akt