Fuller B B, Ehlers S E
Endocrinology. 1984 Jan;114(1):222-6. doi: 10.1210/endo-114-1-222.
Insulin lowers basal levels of tyrosinase activity and inhibits the MSH-induced increase in tyrosinase in Cloudman S-91 mouse melanoma cell cultures. Insulin exerts its inhibitory effects in a typical dose-response manner, with maximal inhibition of enzyme activity occurring at 10-7 M. At maximal inhibition, tyrosinase activity is reduced to approximately 50% of the control levels. This inhibition precedes the observed inhibitory effect on cellular proliferation. Insulin not only lowers cell responsiveness to MSH, but also inhibits the tyrosinase stimulation produced by either theophylline or (Bu)2cAMP. Neither control levels nor MSH-mediated elevated cellular levels of cAMP were altered by insulin (10-7 M). These findings suggest that insulin exerts its inhibitory effects at a site distal to cAMP production. The inhibitory effect of insulin on tyrosinase activity could not be mimicked by either (Bu)2cGMP or 8-bromo-cGMP, suggesting that insulin does not exert its effects by altering cellular levels of this nucleotide. Insulin reduces the rate of incorporation of [3H]leucine into trichloroacetic acid-precipitable material by 50%, a finding which suggests that insulin may exert its inhibitory effects on tyrosinase activity and perhaps on cellular proliferation by causing a general reduction in protein synthetic rates.
胰岛素可降低酪氨酸酶活性的基础水平，并抑制促黑素（MSH）诱导的Cloudman S-91小鼠黑素瘤细胞培养物中酪氨酸酶的增加。胰岛素以典型的剂量反应方式发挥其抑制作用，在10^-7 M时酶活性受到最大抑制。在最大抑制时，酪氨酸酶活性降低至对照水平的约50%。这种抑制作用先于对细胞增殖的抑制作用出现。胰岛素不仅降低细胞对MSH的反应性，还抑制茶碱或（Bu）2cAMP所产生的酪氨酸酶刺激。胰岛素（10^-7 M）既不改变对照水平，也不改变MSH介导的细胞内cAMP水平升高。这些发现表明，胰岛素在cAMP产生的远端位点发挥其抑制作用。胰岛素对酪氨酸酶活性的抑制作用不能被（Bu）2cGMP或8-溴-cGMP模拟，这表明胰岛素不是通过改变这种核苷酸的细胞水平来发挥作用的。胰岛素使[3H]亮氨酸掺入三氯乙酸沉淀物质的速率降低50%，这一发现表明胰岛素可能通过导致蛋白质合成速率普遍降低，从而对酪氨酸酶活性以及可能对细胞增殖发挥抑制作用。
