Martin H, Martin R
Institute of Clinical Chemistry, Karl Marx University Leipzig, GDR.
Gerontology. 1988;34(1-2):48-54. doi: 10.1159/000212930.
The maximal glucocorticoid responsiveness and the adaptation degree are reduced in old rat liver as demonstrated by cortisol stimulation of RNA polymerases. Nevertheless the concentration of unoccupied 3H-dexamethasone binding sites in molybdate-stabilized cytosol of adrenalectomized old animals is significantly increased in comparison with young adult rats. The KD constants showed an increasing tendency, but not a significant one. In the molybdate-free cytosol the results are similar. First studies of the binding kinetics in the molybdate-free system showed a sigmoidal saturation curve in the cytosol of young adult rats, but usual hyperbolic saturation kinetics in the cytosol of old animals. The Hill coefficient was 1.0 +/- 0.1 for old and 1.9 +/- 0.3 for young animals. The binding of activated 3H-dexamethasone receptor complexes to liver nuclei showed no significant age-dependent differences in binding kinetics, acceptor site concentration or affinity. Attention must be paid to altered glucocorticoid receptor binding in the cytosol and in nuclei as a potential cause of changes in hormone-induced gene expression at the pretranscriptional level.
通过皮质醇对RNA聚合酶的刺激表明，老年大鼠肝脏中的最大糖皮质激素反应性和适应程度降低。然而，与年轻成年大鼠相比，去肾上腺老年动物的钼酸盐稳定胞质溶胶中未占据的3H-地塞米松结合位点浓度显著增加。KD常数呈增加趋势，但不显著。在无钼酸盐的胞质溶胶中，结果相似。对无钼酸盐系统中结合动力学的初步研究表明，年轻成年大鼠的胞质溶胶中呈S形饱和曲线，而老年动物的胞质溶胶中则呈现常见的双曲线饱和动力学。老年动物的希尔系数为1.0±0.1，年轻动物为1.9±0.3。活化的3H-地塞米松受体复合物与肝细胞核的结合在结合动力学、受体位点浓度或亲和力方面未显示出明显的年龄依赖性差异。必须注意胞质溶胶和细胞核中糖皮质激素受体结合的改变，这可能是转录前水平激素诱导基因表达变化的潜在原因。
