Kline E L, Carland K, Smith T J
Endocrinology. 1986 Nov;119(5):2118-23. doi: 10.1210/endo-119-5-2118.
Investigations with mouse melanoma B16/C3 cell cultures have suggested that imidazole or a derivative thereof can facilitate expression of the tyrosinase (EC 1.14.18.1) structural gene. The induction of tyrosinase expression by imidazole was inhibited by T3 about 4-fold. When T3 (10 nM) was present for 19 h in proliferating B16/C3 cultures, basal activity of this enzyme was inhibited by approximately 60%. Neither T3 nor imidazole directly affected tyrosinase enzymatic activity in broken cell preparations. Addition of T3 to imidazole-induced cultures rapidly decreased tyrosinase expression (within 30 min) which remained repressed for at least 4 h before recovering. Recovery of tyrosinase activity could be blocked by readdition of hormone. The hormone effect was detectable at 1 nM and was maximal at 10 nM. Removal of supplemental T3 from the medium rapidly reversed the repression of tyrosinase activity. The biologically inactive analog rT3 (10 nM) failed to inhibit basal enzyme activity or alter the imidazole effect on tyrosinase expression. The experimental results with protein and RNA inhibitors indicate that the T3 response is independent of destabilizing the putative transcript for tyrosinase or altering the posttranslational events responsible for its synthesis.
对小鼠黑色素瘤B16/C3细胞培养物的研究表明，咪唑或其衍生物可促进酪氨酸酶（EC 1.14.18.1）结构基因的表达。咪唑对酪氨酸酶表达的诱导作用被T3抑制了约4倍。当在增殖的B16/C3培养物中存在10 nM的T3达19小时时，该酶的基础活性被抑制了约60%。在破碎细胞制剂中，T3和咪唑均未直接影响酪氨酸酶的酶活性。向咪唑诱导的培养物中添加T3会迅速降低酪氨酸酶的表达（在30分钟内），这种抑制至少持续4小时后才恢复。重新添加激素可阻断酪氨酸酶活性的恢复。在1 nM时可检测到激素效应，在10 nM时效应最大。从培养基中去除补充的T3会迅速逆转酪氨酸酶活性的抑制。无生物学活性的类似物反T3（10 nM）未能抑制基础酶活性或改变咪唑对酪氨酸酶表达的影响。使用蛋白质和RNA抑制剂的实验结果表明，T3的反应与破坏酪氨酸酶的假定转录本稳定性或改变负责其合成的翻译后事件无关。
