Slominski Andrzej, Tobin Desmond J, Shibahara Shigeki, Wortsman Jacobo
Dept. of Pathology, Suite 599, University of Tennessee Health Science Center, 930 Madison Avenue, Memphis, TN 38163, USA.
Physiol Rev. 2004 Oct;84(4):1155-228. doi: 10.1152/physrev.00044.2003.
Cutaneous melanin pigment plays a critical role in camouflage, mimicry, social communication, and protection against harmful effects of solar radiation. Melanogenesis is under complex regulatory control by multiple agents interacting via pathways activated by receptor-dependent and -independent mechanisms, in hormonal, auto-, para-, or intracrine fashion. Because of the multidirectional nature and heterogeneous character of the melanogenesis modifying agents, its controlling factors are not organized into simple linear sequences, but they interphase instead in a multidimensional network, with extensive functional overlapping with connections arranged both in series and in parallel. The most important positive regulator of melanogenesis is the MC1 receptor with its ligands melanocortins and ACTH, whereas among the negative regulators agouti protein stands out, determining intensity of melanogenesis and also the type of melanin synthesized. Within the context of the skin as a stress organ, melanogenic activity serves as a unique molecular sensor and transducer of noxious signals and as regulator of local homeostasis. In keeping with these multiple roles, melanogenesis is controlled by a highly structured system, active since early embryogenesis and capable of superselective functional regulation that may reach down to the cellular level represented by single melanocytes. Indeed, the significance of melanogenesis extends beyond the mere assignment of a color trait.
皮肤黑色素在伪装、拟态、社交沟通以及抵御太阳辐射的有害影响方面发挥着关键作用。黑色素生成受到多种因素的复杂调控,这些因素通过受体依赖性和非依赖性机制激活的途径相互作用,以激素、自分泌、旁分泌或内分泌的方式发挥作用。由于黑色素生成调节剂具有多向性和异质性,其控制因素并非简单地排列成线性序列,而是在一个多维网络中相互作用,具有广泛的功能重叠,连接方式既有串联也有并联。黑色素生成最重要的正向调节因子是黑素皮质素1受体(MC1受体)及其配体促黑素细胞激素和促肾上腺皮质激素(ACTH),而在负向调节因子中,刺鼠蛋白尤为突出,它决定了黑色素生成的强度以及合成的黑色素类型。在皮肤作为应激器官的背景下,黑色素生成活性作为有害信号的独特分子传感器和转换器,以及局部稳态的调节因子发挥作用。与这些多种作用相一致,黑色素生成由一个高度结构化的系统控制,该系统自胚胎早期发育就开始活跃,能够进行超选择性功能调节,甚至可以深入到单个黑素细胞所代表的细胞水平。事实上,黑色素生成的意义远不止于赋予一种颜色特征。