Gehring U, Ho A D
Klin Wochenschr. 1987 Mar 16;65(6):247-52. doi: 10.1007/BF01773441.
A generalized view on the mechanism of steroid hormone action is presented with special emphasis on glucocorticoids and their lymphocytolytic effects. The present knowledge on the structure and function of glucocorticoid receptors is reviewed. Following hormone binding, the receptor complex is activated to a form which is able to interact with chromatin or DNA. Several types of receptor mutants have been obtained in an animal cell culture system which allows selection of cell variants. The biochemical analysis of these mutants helped to establish a domain model of receptor structure. The quantitative effect of receptor numbers and hormone activity on lymphocytolysis is described in a cell culture model system and the results are discussed in view of the rational treatment of lymphoid neoplasia with glucocorticoids. The clinical experience with glucocorticoids alone and in combination therapy with cytostatic drugs is summarized. Our special emphasis is on acute lymphoblastic leukemia and malignant lymphoma as patients with these diseases can now be treated with remarkable success rates.
本文提出了关于类固醇激素作用机制的一般性观点,特别强调了糖皮质激素及其淋巴细胞溶解作用。回顾了目前关于糖皮质激素受体结构和功能的知识。激素结合后,受体复合物被激活为一种能够与染色质或DNA相互作用的形式。在动物细胞培养系统中获得了几种类型的受体突变体,该系统允许选择细胞变体。对这些突变体的生化分析有助于建立受体结构的结构域模型。在细胞培养模型系统中描述了受体数量和激素活性对淋巴细胞溶解的定量影响,并根据用糖皮质激素合理治疗淋巴样肿瘤的观点对结果进行了讨论。总结了单独使用糖皮质激素以及与细胞毒性药物联合治疗的临床经验。我们特别关注急性淋巴细胞白血病和恶性淋巴瘤,因为患有这些疾病的患者现在可以得到显著的成功率治疗。