Binding of melanotropic hormones to the melanocortin receptor MC1R on human melanocytes stimulates proliferation and melanogenesis.
Binding of melanotropic hormones to the melanocortin receptor MC1R on human melanocytes stimulates proliferation and melanogenesis.
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DOI：
10.1210/endo.137.5.8612494
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发表时间：
1996-05
期刊：
影响因子：
4.8
通讯作者：
I. Suzuki;R. Cone;S. Im;J. Nordlund;Z. Abdel‐Malek
中科院分区：
文献类型：
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作者：
I. Suzuki;R. Cone;S. Im;J. Nordlund;Z. Abdel‐Malek
α-促黑素细胞激素（α-MSH）和ACTH增加培养的人黑素细胞的增殖和黑素生成。为了进一步分析促黑激素如何产生这些生物学效应，我们使用北方印迹分析研究了α-MSH和ACTH对黑皮质素受体MC 1 R表达的调节，并确定了受体对结构相似肽α-MSH、ACTH、β-MSH和γ-MSH的相对亲和力。我们还测定了这些激素刺激cAMP形成、酪氨酸酶活性和黑素细胞增殖的相对效力。在这些测定中，所述促黑素蛋白的亲和力和效力的顺序为α-MSH = ACTH > β-MSH> γ-MSH。由于这些促黑素的MC 1 R的结合亲和力与其刺激人黑素细胞增殖和黑素生成的能力相关，我们得出结论，这些效果是由MC 1 R的结合和激活特异性介导的。γ-MSH刺激cAMP形成而不影响增殖或黑素生成。然而，我们发现，相对于α-MSH，γ-MSH对cAMP形成的影响是短暂的。我们的研究结果表明，α-MSH，促肾上腺皮质激素，可能β-MSH，但不是γ-MSH，能够在调节人类色素沉着的生理作用，在人类皮肤中的黑素细胞是这些激素的特定目标。
alpha-Melanocyte stimulating hormone (alpha-MSH) and ACTH increase the proliferation and melanogenesis of cultured human melanocytes. To further analyze how melanotropins produce these biological effects, we investigated the regulation of the melanocortin receptor MC1R expression by alpha-MSH and ACTH using Northern blot analysis and determine the relative affinity of the receptor for the structurally similar peptides alpha-MSH, ACTH, beta-MSH, and gamma-MSH. We also determined the relative potencies of these hormones to stimulate cAMP formation, tyrosinase activity, and melanocyte proliferation. The order of affinity and potency of the noted melanotropins in these assays were alpha-MSH = ACTH > beta-MSH > gamma-MSH. Because the binding affinity of each of these melanotropins for the MC1R correlated with its ability to stimulate human melanocyte proliferation and melanogenesis, we conclude that these effects are mediated specifically by binding to and activation of the MC1R. gamma-MSH stimulated cAMP formation without affecting proliferation or melanogenesis. However, we found that relative to alpha-MSH, the effect of gamma-MSH on cAMP formation was transient. Our results suggest that alpha-MSH, ACTH, and possibly beta-MSH, but not gamma-MSH, are capable of a physiological role in regulating human pigmentation, and that melanocytes in human skin are a specific target for these hormones.