The superpotent and ultranrolongecL melanotropic properties of an -melanotropin analog, [Nle4, D-Phe]-MSH, were investigated in a Cloudman S91 (CCL 53.1) melanoma cell line. [Nle4, D-Phe]-MSH is 100-fold more effective than the native hormone, -melanocyte stimulating hormone (-MSH), in stimulating melanoma cell tyrosinase 1. activity. as determined from their minimum effective doses (10 M and 10 M, respectively). [Nle4, D-Phe7]-MSH also exhibits a more sustained effect than -MSH on tyrosinase after removal of the melanotropins from the incubation medium. When cells were exposed to -MSH (10 M) för 24 h, residual activity after removal of the hormone was minimally signifleant.7 In contrast, under the same experimental conditions [Nle4, D-Phe7]-MSH treatment induced tyrosinase activity 2-3 fold above basal level, and maintained remarkable stimulatory effects up to 72 h following melanotropin removal. When the exposure time to melanotropins was reduced to 4 h, -MSH failed to elicit significant tyrosinase activity, whereas [Nle4, D-Phe7]-MSH stimulated significant tyrosinase activity during the first 24 h subsequent to melanotropin removal. Interestingly, this stimulation by the analog increased at 48 h, reached a maximum at 72 h following removal of the melanotropin analog, and remained significantly stimulated för 6 consecutive days in the absence of the analog.
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