Stimulation of the receptor for melanocyte-stimulating hormone by retinoic acid.
Treatment of Cloudman S91 melanoma cells with retinoic acid (RA) inhibits MSH-induced tyrosinase activity and melanin formation [(1990) J. Invest. Dermatol. 94, 461-464]. We report here, however, that in spite of inhibiting MSH-induced pigmentation, RA treatment caused a marked increase in MSH binding capacity for both cell surface and internal MSH binding sites. The stimulation was dose- and time-dependent and reversible, with half-maximal effects seen at 2 microM RA. Stimulation of MSH binding was seen as early as 3 h after exposure of cells to RA. Cell surface and internal binding activity increased in concert. Scatchard analysis indicated that increased MSH binding resulted from a 3-4-fold increase in the number of sites with no significant difference in their affinity for MSH. It appears that in suppressing MSH-induced melanogenesis, RA elicited a compensatory up-regulation of the MSH receptor system.
Chakraborty
A K
AK
Department of Dermatology, Yale University School of Medicine, New Haven, CT 06510.
Orlow
S J
SJ
Pawelek
J M
JM
D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D007700:Kinetics; D009074:Melanocyte-Stimulating Hormones / Q000378:metabolism*; D008546:Melanoma, Experimental; D051379:Mice; D011979:Receptors, Pituitary Hormone / Q000187:drug effects / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology*
D011979:Receptors, Pituitary Hormone; D014212:Tretinoin; C029446:MSH receptor; D009074:Melanocyte-Stimulating Hormones