Changes in the sedimentation properties of cytosolic androgen receptors associated with activation in vitro and in vivo

Abstract

In cell-free systems androgen receptor (AR) labeled with ( 3H) DHT at 0°C in the presence of 50mM molybdate remains unactivated (<3% binding to nuclei) and untransformed (7–8S on sucrose density gradients containing however, these complexes undergo activation and transformation even at 0°C, albeit, very slowly. Incubation of unactivated, untransformed AR complexes at 18°C, or at 0°C in the presence of 0.4M KCl, greatly accelerated both activation and transformation. Activation and transformation are also associated with formation of high affinity ( 3H) DHT-receptor complexes as indicated by decreased rates of ( 3H) DHT dissociation from the receptor. Cytosolic AR complexes labeled with ( 3H) DHT in tissue slices at 37°C, or in vivo, undergo rapid activation, transformation and nuclear translocation. The data suggest that activation and transformation of cytosolic AR in cellfree systems is associated with changes in the physicochemical properties of AR similar to those occurring upon hormone binding in intact cells and in vivo.