Mitogenic and Melanogenic Stimulation of Normal Human Melanocytes by Melanotropic Peptides

• Published in: Proceedings of the National Academy of Sciences - PNAS 1995-02, Vol.92 (5), p.1789-1793
• Main Authors: Abdel-Malek, Zalfa, Swope, Viki B., Suzuki, Itaru, Akcali, Can, Harriger, M. Dana, Boyce, Steven T., Urabe, Kazunori, Hearing, Vincent J.
• Format: Article
• Language: English
• Subjects: Adrenocorticotropic Hormone - pharmacology; alpha-MSH - pharmacology; Cell Division - drug effects; Cells, Cultured; Cellular biology; Cholera; Gene Expression; Hormonal regulation; Hormones; Humans; Intramolecular Oxidoreductases; Isomerases - genetics; Melanins - biosynthesis; Melanocytes; Melanocytes - cytology; Melanocytes - drug effects; Membrane Glycoproteins; Messenger RNA; Mitogens; Monophenol Monooxygenase - genetics; Monophenol Monooxygenase - metabolism; Oxidoreductases; Peptides; Pigmentation; Proteins - genetics; Proteins - metabolism; Receptors; RNA, Messenger - genetics; Skin; Skin Pigmentation - drug effects; Toxins; Tyrosine 3-Monooxygenase - metabolism
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.92.5.1789

The significance of melanotropic hormones as physiologic regulators of cutaneous pigmentation in humans is still controversial. Until recently, no direct effect for melanotropins could be demonstrated on human melanocytes. Here we present conclusive evidence that α-melanotropin (α-melanocyte-stimulating hormone, α-MSH) and the related hormone corticotropin (adrenocorticotropic hormone, ACTH) stimulate the proliferation and melanogenesis of human melanocytes maintained in culture in a growth medium lacking any AMP inducer. The minimal effective dose of either hormone is 0.1 nM. In time-course experiments, the increase in cell number and tyrosinase activity became evident after one treatment of the melanocytes with 100 nM α-MSH for 48 hr. The mitogenic effect gradually increased to 50-270% above control, depending on the individual melanocyte strain, with continuous treatment with 100 nM α-MSH for 8 days, whereas the melanogenic effect became maximal (70-450% increase above control) after 4 days of treatment. Western blot analysis of tyrosinase and the tyrosinase-related proteins TRP-1 and TRP-2 revealed that α-MSH increased the expression of those three melanogenic proteins. This was not accompanied by any change in their mRNA levels after brief (1.5-24 hr) or prolonged (6 days) treatment with 100 nM α-MSH, suggesting that the increased expression of these melanogenic proteins was due to posttranscriptional events. These results demonstrate both mitogenic and melanogenic effects of α-MSH and ACTH on human melanocytes. That both hormones are effective at subnanomolar concentrations, combined with the presence of melanotropin receptors on human melanocytes, strongly suggests that these melanotropins play a physiologic role in regulating human cutaneous pigmentation.