Original Article

Journal of Investigative Dermatology (1988) 91, 106–113; doi:10.1111/1523-1747.ep12464093

Induction of Melanization Within Hair Bulb Melanocytes in Chinchilla Mutant by Melanogenic Stimulants

Genji Imokawa, Yukihiko Yada and Yoshiaki Hori

Tochigi Research Laboratories, Kao Corporation, Tochigi, and Department of Dermatology, Yamanashi Medical College, Yamanashi, Japan

Received 10 September 1987; Accepted 13 January 1988.

Top

Abstract

In an attempt to clarify the mechanisms underlying the lack of melanin formation in hair bulb melanocytes of chinchilla mice (genotype a/a, cch/cch, strain PW), we studied the effect of exogenous melanogenic stimulants such as theophylline (Tp), dibutyryl cyclic AMP (db-cAMP), and alpha-melanocyte- stimulating hormone (alpha-MSH) on the induction of melanization. Skin explants excised from the dorsa of chinchilla or lethal yellow C57BL/6J, Aγ/a) mice at 7 to 9 days of age were cultured in the presence of Tp (2 mM), db-cAMP (2 mM), or alpha-MSH (1.0 mug/ml). After 2 to 5 days, melanin formation was induced in hair bulb melanocytes of chinchilla mutant in response to both Tp and db-cAMP, but alpha-MSH did not produce new melanin formation. In contrast, yellow mutant increased the melanin formation in response to all stimulants. Electron microscopic studies demonstrated that while non- treated hair bulb melanocytes of chinchilla mutant contain a large number of stage II-III melanosomes without melanin deposition, a hair bulb treated with Tp exhibits the new formation of melanin within melanosomes that appears both as typical eumelanosomes with striated longitudinal matrices and as pheomelanosomes with vacuolar melanization. Quantitative analysis of melanin has revealed that in chinchilla mutant, Tp and db-cAMP induce a several fold increase in the formation of both eumelanin [pyrrole-2,3,5-tricarboxylic acid (PTCA)] and pheomelanin (aminohydroxyphenylalanine), whereas alpha-MSH does not stimulate production of either melanin. In yellow mutant, db-cAMP induced a remarkable increase in eumelanin (PTCA), in contrast to the fewfold increase induced by alpha-MSH and Tp. All stimulants induced a slight increase in pheomelanin to a similar extent. These different reactions to melanogenic stimulation suggest a possible defect in the tyrosinase activation system within hair bulb melanocytes in chinchilla mutants.

Top

References

  1. Hori, Y, Mizoguchi, M, Kukita, A: Mouse model for tyrosinase-positive oculocutaneous albinism: Tyrosinase activity and ultrastructure of melanocytes, in: Pigment Cell. 1981 Edited by M Seiji. University of Tokyo Press, Tokyo, pp 159–165,
  2. Townsend, D, Witkop, CJ, Mattson, J: Tyrosinase subcellular distribution and kinetic parameters in wild types and c-locus mutant C57BL/6J mice. J Exp Zoo 1981 216: 113–119,
  3. Imokawa, G, Mishima, Y: Loss of melanogenic properties in tyrosinases induced by glycosylation inhibitors within malignant melanoma cells. Cancer Res 1982 42: 1994–2002,  | PubMed | ISI | ChemPort |
  4. Imokawa, G, Mishima, Y: Importance of glycoproteins in the initiation of melanogenesis: An electron microscopic study of B-16 melanoma cells after release from inhibition of glycosylation. J Invest Dermatol 1986 87: 319–325,
  5. Mishima, Y, Imokawa, G: Selective aberration and pigment loss in melanosomes of malignant melanoma cells in vitro by glycosylation inhibitors: Premelanosomes as glycoprotein. J Invest Dermatol 1983 81: 106–114,  | Article | PubMed | ISI | ChemPort |
  6. Imokawa, G, Mishima, Y: Selective aberration of secretory glycoprotein premelanosomes and Golgi cisternae induced by carbohydrate processing inhibitor, monensin. Proc Jpn Soc Invest Dermatol 1985 9: 11–12,
  7. Hu, F, Mah, K, Teramura, DJ: Electron microscopic and cytochemical observation of theophylline and melanocyte-stimulating hormone effect on melanoma cells in culture. Cancer Res 1982 42: 2786–2791,
  8. Davis, BJ: Disc electrophoresis. II. Method and application to human serum properties. Ann NY Acad Sci 1961 121: 404–427,
  9. Ito, S, Fujita, K: Microanalysis of eumelanin and pheomelanin in hair and melanomas by chemical degradation and liquid chromatography. Anal Biochem 1985 144: 527–536,  | Article | PubMed | ISI | ChemPort |
  10. Foster, M: Genetic aspects of mammalian melanogenesis, in Advances in Biology of Skin. VII. The Pigmentary System 1967 Edited by W Montagna, F Hu. Pergamon Press, New York, pp 467–477,
  11. Imokawa, G, Mishima, Y: Functional analysis of tyrosinase isozymes of cultured malignant melanoma cells during the recovery period following interrupted melanogenesis induced by glycosylation inhibitors. J Invest Dermatol 1984 83: 196–201,
  12. Tamate, HB, Takeuchi, T: Action of the e locus of mice in the response of pheomelanotic hair follicles to alpha-melanocyte-stimulating hormone in vitro. Science 1984 224: 1241–1242,
  13. Steinberg, ML, Whittaker, JR: Theophylline incorporation into the nucleic acids of theophylline-stimulated melanoma cells. J Invest Dermatol 1978 71: 250–256,

Extra navigation

.
ADVERTISEMENT