Regulation of human epidermal melanocyte biology by β-endorphin
Regulation of human epidermal melanocyte biology by β-endorphin
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DOI：
10.1046/j.1523-1747.2003.12242.x
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发表时间：
2003-06-01
影响因子：
6.5
通讯作者：
Tobin, DJ
中科院分区：
文献类型：
--
作者：
Kauser, S;Schallreuter, KU;Tobin, DJ
β-内啡肽是从前体阿片黑素皮质素前体中分离出来的一种阿片肽，也可以从中衍生出其他多肽，如促肾上腺皮质激素、β-促脂肪激素和α-黑素细胞刺激素。α-黑素细胞刺激素和促肾上腺皮质激素通过作用于黑素皮质素-1受体来调节人类皮肤色素沉着。虽然据报道，暴露于紫外线辐射后，血浆中的β-内啡肽会增加，但到目前为止，还没有证明β-内啡肽在调节人类表皮黑素细胞生物学中的功能作用。这项研究旨在研究人表皮黑素细胞中β-内啡肽/阿片受体系统的参与。为了解决这个问题，我们使用了逆转录-聚合酶链式反应，免疫组织化学/细胞化学和免疫电子显微镜使用β-内啡肽和Mu-阿片受体特异性抗体。β-内啡肽在表皮黑素细胞培养中的功能作用是通过多肽直接刺激来评估的。本研究证实了在培养的表皮黑素细胞中存在mU-阿片受体基因的表达，以及阿片黑素皮质素原基因的表达。此外，我们还发现，在糖蛋白100阳性的黑素细胞中，β-内啡肽和Mu-阿片受体在蛋白水平上原位表达。β-内啡肽受体和u-阿片受体的表达与其体外分化状态呈正相关。此外，免疫电子显微镜研究显示，β-内啡肽与黑素小体有关。功能研究表明，在没有任何外源阿片黑素原多肽供应的情况下，β-内啡肽在培养的表皮黑素细胞中具有强大的黑素生成、有丝分裂和树突生成作用。因此，我们报道了人类表皮黑素细胞表达一个功能齐全的β-内啡肽/u-阿片受体系统。在没有任何数据显示Mu-阿片受体和黑素皮质素-1受体之间存在相互作用的情况下，我们得出结论，β-内啡肽/Mu-阿片受体系统参与了皮肤色素沉着的调节。
beta-Endorphin is an opioid peptide cleaved from the precursor pro-hormone pro-opiomelanocortin, from which other peptides such as adrenocorticotropic hormone, beta-lipotropic hormone, and alpha-melanocyte-stimulating hormone are also derived. alpha-Melanocyte-stimulating hormone and adrenocorticotropic hormone are well documented to regulate human skin pigmentation via action at the melanocortin-1 receptor. Whereas plasma beta-endorphin is reported to increase after exposure to ultraviolet radiation, to date a functional role for beta-endorphin in the regulation of human epidermal melanocyte biology has not been demonstrated. This study was designed to examine the involvement of the beta-endorphin/mu-opiate receptor system in human epidermal melanocytes. To address this question we employed reverse transcription-polymerase chain reaction, and immunohistochemistry/cytochemistry and immunoelectron microscopy using beta-endorphin and mu-opiate receptor specific antibodies. A functional role for beta-endorphin was assessed in epidermal melanocyte cultures by direct stimulation with the peptide. This study demonstrated the expression of mu-opiate receptor mRNA in cultured epidermal melanocytes, as well as mRNA for pro-opiomelanocortin. In addition, we have shown that beta-endorphin and mu-opiate receptor are expressed at the protein level in situ in glycoprotein100-positive melanocytes. The expression of both beta-endorphin and mu-opiate receptor correlated positively with their differentiation status in vitro. Furthermore, immunoelectron microscopy studies revealed an association of beta-endorphin with melanosomes. Functional studies showed that beta-endorphin has potent melanogenic, mitogenic, and dendritogenic effects in cultured epidermal melanocytes deprived of any exogenous supply of pro-opiomelanocortin peptides. Thus, we report that human epidermal melanocytes express a fully functioning beta-endorphin/mu-opiate receptor system. In the absence of any data showing cross-talk between the mu-opiate receptor and the melanocortin-1 receptor, we conclude that the beta-endorphin/mu-opiate receptor system participates in the regulation of skin pigmentation.