Korean J Dermatol.  1999 Nov;37(11):1589-1595.

The Effects of Endothlin-1 Receptor Antagonists on the Human Melanocyte

• Hwang JY
• Cho MK
• Park YL
• Lee JS
• Whang KU

Abstract

BACKGROUND: Melanocytes synthesize melanin pigment by the action of specific enzyme tyrosinase. In normal skin, melanocytes maintain their constant population and steady melanogenic activity. But several stimuli to the skin such as UV irradiation and chemical irritation may accelerate the proliferation and differentiation of melanocytes and subsequently lead to hyperpigmentation of the skin. Endothelin-1(ET-1), produced by human keratinocyte acts as a strong mitogen on human melanocyte and has an effect on paracrine linkage between keratinocytes and melanocytes, and plays an important role in UVB induced hyperpigmentation as an intrinsic factor.
OBJECTIVE
In this study, the role of ET-1 on melanocyte proliferation and melanogenesis was investigated, and the effects of ETRA(endothelin receptor antagonist) in cultured melanocyte was also evaluated.
METHODS
Primary melanocytes from neonatal foreskins were cultured in complete MCDB 154 medium. To examine the effects of ET-1 on melanocytes, cultuled melanocytes were treated with ET-1 at various concentration(5nM, 10nM, 15nM, 20nM). Three days later, melanocyte proliferation and melanin content were measured. Also, we examined the effects of ETRA on ET-1 treated melanocytes. Five kinds of ETRA were added into 10nM of ET-1 treated melanocyte. After three days cultuviation, inhibitory effect of ETRA on ET-1 activity was measured.
RESULTS
1. The number of melanocytes increased in the groups of incubation with melanocyte medium of concentration in 10nM ET-1 than others. 2. The melanin contents increased most in the groups of incubation with melanocyte medium of concentration in 10nM ET-1 than others. 3. The number of melanocytes decreased in the groups of inhibited with ETRA I. 4. The melanin contents decreased in the groups of inhibited with ETRA II.
CONCLUSION
This study provided an important confirmation of the proposal that ET-1 is intrinsic factor for proliferation and differentiation of human melanocytes, and ETRA has inhibitory effect on ET-1 induced melanogenesis and melanocyte proliferation. These findings suggest that ET-1 is an important mediator in epidermal pigmentation, and we will be able to use ETRA as a new whitening agent.

Keyword

Melanocyte; Endothelin-1; Endothelin-1 receptor antagonist

MeSH Terms

Endothelin-1
Foreskin
Humans*
Hyperpigmentation
Intrinsic Factor
Keratinocytes
Melanins
Melanocytes*
Monophenol Monooxygenase
Pigmentation
Skin
Endothelin-1
Intrinsic Factor
Melanins
Monophenol Monooxygenase