Hunt G, Donatien P D, Lunec J, Todd C, Kyne S, Thody A J
Department of Dermatology, University of Newcastle upon Tyne, United Kingdom.
Pigment Cell Res. 1994 Aug;7(4):217-21. doi: 10.1111/j.1600-0749.1994.tb00052.x.
Although the administration of melanocyte-stimulating hormone (MSH) peptides results in skin darkening in man, cultured human melanocytes have been reported to be unresponsive to these peptides. This may be a consequence of the conditions under which the cells were maintained in vitro, particularly the use of phorbol esters and cholera toxin as melanocyte mitogens. By culturing the cells in the absence of these additives, we demonstrate that alpha-MSH and its synthetic analogue Nle4DPhe7 alpha-MSH (NDP-MSH) induce dose-related increases in melanin content and tyrosinase activity and affect cell morphology in the majority of human melanocyte cultures. In addition, NDP-MSH induces increases in tyrosinase mRNA and tyrosinase-related protein-1 (TRP-1) mRNA. The dose-response curves for the MSH peptides are sigmoidal and the two peptides are equipotent in their effects on human melanocytes. Adrenocorticotropic hormone (ACTH) also affects morphology and stimulates melanogenesis and tyrosinase activity in human melanocytes. However, the dose-response curves for ACTH are biphasic, and the melanocytes respond to lower concentrations of ACTH than MSH peptides, similar to those normally present in human plasma. These findings may be important in understanding the role of these pro-opiomelanocortin peptides in human skin pigmentation.
尽管给予促黑素细胞激素（MSH）肽会导致人类皮肤变黑，但据报道，培养的人黑素细胞对这些肽无反应。这可能是细胞在体外培养条件的结果，特别是使用佛波酯和霍乱毒素作为黑素细胞有丝分裂原。通过在无这些添加剂的情况下培养细胞，我们证明α-MSH及其合成类似物Nle4DPhe7α-MSH（NDP-MSH）在大多数人黑素细胞培养物中诱导黑素含量和酪氨酸酶活性呈剂量相关增加，并影响细胞形态。此外，NDP-MSH诱导酪氨酸酶mRNA和酪氨酸酶相关蛋白-1（TRP-1）mRNA增加。MSH肽的剂量反应曲线呈S形，这两种肽对人黑素细胞的作用等效。促肾上腺皮质激素（ACTH）也影响人黑素细胞的形态并刺激黑素生成和酪氨酸酶活性。然而，ACTH的剂量反应曲线是双相的，并且黑素细胞对ACTH的反应浓度低于MSH肽，类似于人血浆中通常存在的值。这些发现对于理解这些阿片促黑素皮质素原肽在人类皮肤色素沉着中的作用可能很重要。
