The human melanocyte stimulating hormone receptor has evolved to become "super-sensitive" to melanocortin peptides

Mol Cell Endocrinol. 1994 Jun;102(1-2):R7-11. doi: 10.1016/0303-7207(94)90113-9.


Melanocyte-stimulating hormone (MSH) stimulates pigmentation in mammals by activating specific cell surface MSH receptors (MC1-Rs) on melanocytes. MC1-Rs on normal human melanocytes have been difficult to detect and characterise. The pharmacological characterisation of a cloned human MC1-R (hMC1-R) is reported here, and directly compared with that of a cloned mouse MC1-R (mMC1-R). The human and mouse MC1-Rs are equally sensitive (EC50 = 1-2 pM) to the super potent analogue of alpha-MSH, NDP-MSH. In contrast with the mMC1-R, the hMC1-R is also very sensitive to alpha-MSH (EC50 = 2 pM), ACTH (EC50 = 8 pM), and Lys gamma 3-MSH (EC50 < 10(-10) M). This suggests that in man, in contrast with rodents, both ACTH and Lys gamma 3-MSH may have physiological roles in pigmentation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenylyl Cyclases / biosynthesis
  • Adenylyl Cyclases / drug effects
  • Animals
  • Base Sequence
  • Cells, Cultured
  • DNA, Complementary
  • Humans
  • Melanocyte-Stimulating Hormones / pharmacology*
  • Mice
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Receptors, Pituitary Hormone / drug effects
  • Receptors, Pituitary Hormone / genetics*
  • Receptors, Pituitary Hormone / metabolism


  • DNA, Complementary
  • Receptors, Pituitary Hormone
  • MSH receptor
  • Melanocyte-Stimulating Hormones
  • Adenylyl Cyclases