EFFECTS OF TAMOXIFEN ON THE BINDING AND METABOLISM OF TESTOSTERONE BY HUMAN PROSTATIC TISSUE AND PLASMA INVITRO

The in-vitro metabolism of testosterone in benign and malignant prostatic tissue was examined and distinct quantitative differences between the two types of specimens were observed. The major metabolite of testosterone in the hyperplastic prostate was 5α-dihydro-testosterone and a high 3α(β)-hydroxysteroid dehydrogenase activity was also detected. In the malignant tissue, 5α-reductase activity was considerably reduced and there was little or no androstanediol formed; the 17β-dehydrogenase activity was, however, higher than in the benign tissue. The decrease in 5α-reductase was always followed by a compensatory change in the 3α(β)-hydroxysteroid dehydrogenase of the malignant prostate. The present study revealed that the ratio of the mean activities of 5α-reductase to 3α(β)-hydroxysteroid dehydrogenase in the two types of specimen always remained a constant. Although the antioestrogen, tamoxifen, induced an inhibitory effect on the activities of 5α-reductase and 17β-hydroxysteroid dehydrogenase in the gland, the present investigation also suggested that tamoxifen stimulated the activity of 3α(3β)-hydroxysteroid dehydrogenase. In blood, the action of tamoxifen appeared to be confined to the displacement of androgens from the binding sites on the sex hormone binding globulin.