Stimulation of S91 melanoma tyrosinase activity by superpotent α-melanotropins

Mohamed M. Marwan, Zalfa A. Abdel Malek, Kristie L. Kreutzfeld, Mac E. Hadley, Brian C. Wilkes, Victor J. Hruby, Ana Maria de L. Castrucci

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

α-Melanocyte-stimulating hormone (α-MSH, α-melanotropin), [Nle4,D-Phe7]-α-MSH and related fragment analogues, Ac-[Nle4,D-Phe7]-α-MSH4-11-NH2 and Ac-[Nle4,D-Phe7]-α-MSH4-10-NH2, were studied for their ability to stimulate tyrosinase activity in Cloudman S91 mouse melanoma cells in tissue culture. All of the melanotropins stimulated tyrosinase activity in a dose-dependent manner. [Nle4,D-Phe7]-α-MSH was about 100 times more active than a-MSH as determined from the minimal effective dose (MED) required to activate the enzyme above control (basal) levels. The MED of this analogue to significantly stimulate tyrosinase activity at 24, 48 and 72 h of incubation was 10-11 M whereas the MED of α-MSH was 10-9 M at each of these times. The maximum tyrosinase activity achieved from the time of initial incubation in the presence of [Nle4,D-Phe7]-α-MSH was approximately 3-, 5- and 6-fold greater than control levels at 24, 48 and 72 h, respectively. The 2 [Nle4,D-Phe7]-substituted fragment analogues were at least as active as the tridecapeptide analogue and therefore at least 100-fold more active than a-MSH in stimulating enzyme activity. These [Nle4,D-Phe7]-substituted analogues were more active in the melanoma tyrosinase assay than in the melanoma adenylate cyclase assay or other normal melanocyte (frog and lizard skin) bioassays.

Original languageEnglish (US)
Pages (from-to)171-177
Number of pages7
JournalMolecular and Cellular Endocrinology
Volume41
Issue number2-3
DOIs
StatePublished - Jul 1985

Keywords

  • MSH
  • melanin
  • melanocyte-stimulating hormone
  • melanogenesis
  • melanotropin
  • tyrosinase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

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