Steroid Receptor Recycling and Interaction of Receptor with RNA

Steroid receptors, such as the androgen receptor from the rat ventral prostate, are involved in a recycling process as part of the mechanism by which steroids affect target tissues. Recycling of steroid-receptor complexes may involve interaction of receptors with RNA. Evidence for RNA-receptor complexes in various cells and tissues has been presented, and it has been shown that the ability of RNA to interact with steroid-receptor complexes is dependent on the composition of the RNA. As part of our investigations on the role of RNA in steroid-receptor recycling, we have studied the effects of actinomycin D and cordycepin (3'-deoxyadenosine) on androgen receptors in short-term cultures of rat ventral prostate tissue. Actinomycin D increased nuclear and decreased cytoplasmic levels of androgen-receptor complexes. Cordycepin, in contrast, decreased nuclear and increased cytoplasmic levels of androgen-receptor complexes. Cordycepin markedly decreased the amount of cytosolic androgen-receptor complex that could bind to DNA-cellulose whereas actinomycin D had no effect on DNA-cellulose binding activity. Although both actinomycin D and cordycepin are inhibitors of RNA synthesis, the contrasting effects of cordycepin may be due to inhibition of RNA processing or transport by cordycepin. The effects of these two compounds are consistent with a model of steroid receptor recycling in which RNA facilitates removal of receptors from the nuclear acceptor and the steroid receptor remains associated with the RNA during RNA processing and transport.