Karin M, Herschman H R
J Cell Physiol. 1980 Apr;103(1):35-40. doi: 10.1002/jcp.1041030106.
HeLa cells grown in chemically defined medium lacking glucocorticoids synthesize metallothioneins, low molecular-weight heavy-metal binding proteins. Dexamethasone and hydrocortisone increase the rate of metallothionein synthesis five- to ten-fold. Maximal induction is achieved with 10(-8)M dexamethasone and 10 (-7)M hydrocortisone. Half-maximal induction is achieved at 5 X 10(-9)M dexamethasone and 5 X 10(-8)M hydrocortisone. Although carried for many generations in the absence of any glucocorticoids, HeLa cells (clone S) contain 25,000 specific 3H-dexamethasone receptors that translocate into the nucleus after one hour of incubation. 3H-dexamethasone binds to a single class of receptors with an apparent Kd = 18.8 nM. A variety of steroids can be classified into three classes, based on their effect on metallothionein synthesis: (a) full agonists (optimal inducers), (b) intermediate effectors which have either partial agonist or antagonist activities, and (c) inactive steroids. There is a correlation between the effects on metallothionein synthesis of different steroids and their ability to compete with 3H-dexamethasone binding. We conclude that metallothionein is induced in HeLa cells by a glucocorticoid receptor mediated mechanism.
在缺乏糖皮质激素的化学限定培养基中生长的海拉细胞会合成金属硫蛋白，即低分子量重金属结合蛋白。地塞米松和氢化可的松可使金属硫蛋白的合成速率提高5至10倍。10(-8)M地塞米松和10(-7)M氢化可的松可实现最大诱导作用。在5×10(-9)M地塞米松和5×10(-8)M氢化可的松时可达到半数最大诱导作用。尽管在没有任何糖皮质激素的情况下传代培养了许多代，但海拉细胞（克隆S）含有25,000个特异性3H-地塞米松受体，孵育1小时后会转移到细胞核中。3H-地塞米松与一类受体结合，其表观解离常数Kd = 18.8 nM。根据它们对金属硫蛋白合成的影响，多种类固醇可分为三类：(a) 完全激动剂（最佳诱导剂），(b) 具有部分激动剂或拮抗剂活性的中间效应剂，以及 (c) 无活性类固醇。不同类固醇对金属硫蛋白合成的影响与其与3H-地塞米松结合的竞争能力之间存在相关性。我们得出结论，海拉细胞中的金属硫蛋白是通过糖皮质激素受体介导的机制诱导产生的。
