Abdel-Malek Z, Swope V B, Suzuki I, Akcali C, Harriger M D, Boyce S T, Urabe K, Hearing V J
Department of Dermatology, University of Cincinnati College of Medicine, OH 45267-0592.
Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1789-93. doi: 10.1073/pnas.92.5.1789.
The significance of melanotropic hormones as physiologic regulators of cutaneous pigmentation in humans is still controversial. Until recently, no direct effect for melanotropins could be demonstrated on human melanocytes. Here we present conclusive evidence that alpha-melanotropin (alpha-melanocyte-stimulating hormone, alpha-MSH) and the related hormone corticotropin (adrenocorticotropic hormone, ACTH) stimulate the proliferation and melanogenesis of human melanocytes maintained in culture in a growth medium lacking any AMP inducer. The minimal effective dose of either hormone is 0.1 nM. In time-course experiments, the increase in cell number and tyrosinase activity became evident after one treatment of the melanocytes with 100 nM alpha-MSH for 48 hr. The mitogenic effect gradually increased to 50-270% above control, depending on the individual melanocyte strain, with continuous treatment with 100 nM alpha-MSH for 8 days, whereas the melanogenic effect became maximal (70-450% increase above control) after 4 days of treatment. Western blot analysis of tyrosinase and the tyrosinase-related proteins TRP-1 and TRP-2 revealed that alpha-MSH increased the expression of those three melanogenic proteins. This was not accompanied by any change in their mRNA levels after brief (1.5-24 hr) or prolonged (6 days) treatment with 100 nM alpha-MSH, suggesting that the increased expression of these melanogenic proteins was due to posttranscriptional events. These results demonstrate both mitogenic and melanogenic effects of alpha-MSH and ACTH on human melanocytes. That both hormones are effective at subnanomolar concentrations, combined with the presence of melanotropin receptors on human melanocytes, strongly suggests that these melanotropins play a physiologic role in regulating human cutaneous pigmentation.
促黑素作为人类皮肤色素沉着生理调节因子的重要性仍存在争议。直到最近，还未能证明促黑素对人类黑素细胞有直接作用。在此，我们提供确凿证据表明，α - 促黑素（α - 黑素细胞刺激素，α - MSH）和相关激素促肾上腺皮质激素（促肾上腺皮质激素，ACTH）可刺激在缺乏任何AMP诱导剂的生长培养基中培养的人类黑素细胞的增殖和黑素生成。两种激素的最小有效剂量均为0.1 nM。在时间进程实验中，用100 nM α - MSH处理黑素细胞48小时一次后，细胞数量和酪氨酸酶活性的增加变得明显。根据个体黑素细胞株的不同，用100 nM α - MSH连续处理8天，促有丝分裂作用逐渐增加至比对照高50 - 270%，而黑素生成作用在处理4天后达到最大（比对照增加70 - 450%）。对酪氨酸酶以及酪氨酸酶相关蛋白TRP - 1和TRP - 2的蛋白质印迹分析表明，α - MSH增加了这三种黑素生成蛋白的表达。在用100 nM α - MSH进行短暂（1.5 - 24小时）或长时间（6天）处理后，它们的mRNA水平没有任何变化，这表明这些黑素生成蛋白表达的增加是由于转录后事件。这些结果证明了α - MSH和ACTH对人类黑素细胞的促有丝分裂和黑素生成作用。这两种激素在亚纳摩尔浓度下均有效，再加上人类黑素细胞上存在促黑素受体，强烈表明这些促黑素在调节人类皮肤色素沉着中发挥生理作用。
