Changes in cytosolic androgen receptor after administration of testosterone of androgen-dependent mouse mammary tumor (Shionogi carcinoma) and its sublines of altered androgen dependency

The effect of testosterone treatment on the cytosolic androgen receptor in an androgen-dependent tumor (Shionogi Carcinoma 115, SC 115) and its sublines of altered hormone-dependency (CS 1, less androgen-dependent, and CS 2, androgen-independent) was examined. In all tumors examined a single, high-affinity binding to 3H-R 1881 was detected in cytosols. The size of the maximum binding sites was in the order SC 115, CS 1 and CS 2. Inhibition experiments revealed that the binding to 3H-R 1881 in cytosols of these tumors was attributable to the androgen receptor. The amount of the androgen receptor in cytosols was decreased at 1 hr after testosterone injection, then replenished gradually towards the pretreatment level. Depletion of the androgen receptor was dependent on the dose of testosterone administered. Multiple injections of testosterone depressed the replenishment of the receptor. Treatment with actinomycin D or cycloheximide did not alter the dynamics of the androgen receptor. Therefore, it was concluded that the depletion and replenishment of the androgen receptor in cytosols of the tumors were caused by receptor recycling. Because a similar pattern of depletion and replenishment of the androgen receptor was also observed in the less androgen-dependent tumors, the growth of tumors was felt to be unrelated to the receptor dynamics.