Cultured Human Melanocytes Respond to MSH Peptides and ACTH

Abstract

Although the administration of melanocyte-stimulating hormone (MSH) peptides results in skin darkening in man, cultured human melanocytes have been reported to be unresponsive to these peptides. This may be a consequence of the conditions under which the cells were maintained in vitro, particularly the use of phorbol esters and cholera toxin as melanocyte mitogens. By culturing the cells in the absence of these additives, we demonstrate that alpha-MSH and its synthetic analogue Nle4DPhe7 alpha-MSH (NDP-MSH) induce dose-related increases in melanin content and tyrosinase activity and affect cell morphology in the majority of human melanocyte cultures. In addition, NDP-MSH induces increases in tyrosinase mRNA and tyrosinase-related protein-1 (TRP-1) mRNA. The dose-response curves for the MSH peptides are sigmoidal and the two peptides are equipotent in their effects on human melanocytes. Adrenocorticotropic hormone (ACTH) also affects morphology and stimulates melanogenesis and tyrosinase activity in human melanocytes. However, the dose-response curves for ACTH are biphasic, and the melanocytes respond to lower concentrations of ACTH than MSH peptides, similar to those normally present in human plasma. These findings may be important in understanding the role of these pro-opiomelanocortin peptides in human skin pigmentation.

FermentedViola mandshuricaInhibits Melanogenesis in B16 Melanoma Cells

“…CEFV was found to inhibit mRNA and protein levels of MITF in a dose-dependent manner, MITF is known as a major transcription factor in the regulation of tyrosinase expression, and thus plays a critical role in melanin biosynthesis. [8][9][10][11] Our results are consistent with the findings of a recent report 37) that xanthohumol (XH) significantly decreased mRNA and protein levels of MITF, suggesting that XH inhibits MITF transcription.…”

“…Moreover, it is well known that -MSH, as a signal transducer, potently induces MITF expression and increases melanin synthesis. [9][10][11] The extracellular signal-regulated kinase (ERK) signaling pathway plays a crucial role in cell proliferation and differentiation. 12) It has been reported that inhibition of the ERK pathway induces B16 melanoma cell differentiation and increases tyrosinase activity, suggesting that the pathway regulates melanogenesis.…”

High expression of PKA regulatory subunit 1A protein is related to proliferation of human melanoma cells

“…The cAMP-PKA pathway is the major signal transduction pathway involved in melanocyte-stimulating hormone receptor-mediated signaling, melanin production and melanocyte differentiation (Levine et al, 1991;Hunt et al, 1994), although its role in controlling melanocyte proliferation is still controversial. Indeed, a-melanocyte-stimulating hormone (MSH) was shown to stimulate melanocyte proliferation in vitro (De Luca et al, 1993), even if many data indicate an antiproliferative role of cAMP in these cells (Dumaz and Marais, 2005).…”

Melanocyte Receptors: Clinical Implications and Therapeutic Relevance

“…Of those, the most important role in the regulation of the melanocyte behavior is played by MCR1. Although there are reports showing MCR2 expression on melanocytes [46,47], its role in normal and malignant melanocytes is unclear.Concerning β-endorphin, recent reports have shown that the cutaneous β-endorphin/μ-opiate receptor system is functionally active via its ability to up-regulate melanocyte dendricity, proliferation, and pigmentation [48]. …”