Regulation of eumelanin/pheomelanin synthesis and visible pigmentation in melanocytes by ligands of the melanocortin 1 receptor
Regulation of eumelanin/pheomelanin synthesis and visible pigmentation in melanocytes by ligands of the melanocortin 1 receptor
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DOI：
10.1111/j.1755-148x.2008.00479.x
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发表时间：
2008-08-01
影响因子：
4.3
通讯作者：
Hearing, Vincent J.
中科院分区：
文献类型：
--
作者：
Le Pape, Elodie;Wakamatsu, Kazumasa;Hearing, Vincent J.
头发和皮肤中黑色素的产生受到黑皮质素 1 受体 (MC1R) 的严格调节，其激活由两种分泌配体 α-黑素细胞刺激激素 (α MSH) 和刺豚鼠信号蛋白 (ASP) 控制。由于黑色素在生物组织中极其稳定、持续数年，因此 ASP 引起的可见色素沉着相对快速减少的机制引起了人们的极大兴趣。在本研究中，在正常小鼠黑色素细胞中评估了 ASP 和 α MSH 对黑色素合成调节和可见色素沉着的影响，并与酪氨酸酶抑制剂苯硫脲 (PTU) 的快速脱色效果进行了比较。在 4 天的治疗中，α MSH 在增加真黑素含量之前先增加了褐黑素水平。相反，ASP 关闭了色素合成途径，在治疗 1 天内减少了真黑色素和偏黑色素的合成，这与酪氨酸酶蛋白水平和活性的降低成正比。这些结果表明，ASP 诱导的黑素细胞可见脱色并不需要现有黑色素的降解，而是由于黑素细胞更新对现有黑色素的稀释，这强调了色素分布对可见颜色的重要性。
The production of melanin in the hair and skin is tightly regulated by the melanocortin 1 receptor (MC1R) whose activation is controlled by two secreted ligands, alpha-melanocyte stimulating hormone (alpha MSH) and agouti signal protein (ASP). As melanin is extremely stable, lasting years in biological tissues, the mechanism underlying the relatively rapid decrease in visible pigmentation elicited by ASP is of obvious interest. In this study, the effects of ASP and alpha MSH on the regulation of melanin synthesis and on visible pigmentation were assessed in normal murine melanocytes and were compared with the quick depigmenting effect of the tyrosinase inhibitor, phenylthiourea (PTU). alpha MSH increased pheomelanin levels prior to increasing eumelanin content over 4 days of treatment. Conversely, ASP switched off the pigment synthesis pathway, reducing eu- and pheo-melanin synthesis within 1 day of treatment that was proportional to the decrease in tyrosinase protein level and activity. These results demonstrate that the visible depigmentation of melanocytes induced by ASP does not require the degradation of existing melanin but rather is due to the dilution of existing melanin by melanocyte turnover, which emphasizes the importance of pigment distribution to visible color.