Some aspects of dexamethasone binding in the old rat liver

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.