Effect of tamoxifen on stromal protein synthesis in the human prostate

To test the hypothesis that estrogen may have significant biological effects on the human prostate, we studied the effects of in vivo administration of tamoxifen, an antiestrogen, on human prostatic stromal protein synthesis in vitro. This was done by measuring [3H]proline incorporation in vitro in stromal cells separated enzymatically with 0.5% collagenase and trypsin from hypertrophic prostatic tissue removed at surgery. A mechanical method for separation of epithelium and stroma was attempted, but cell damage resulted in very low incorporation of [3H]proline into protein. Twelve patients were given 20 mg tamoxifen twice daily for 10 days before surgery. The serum levels of tamoxifen at the time of surgery ranged from 200-500 pmol/ml. Control tissues (14) were obtained from untreated patients. Tamoxifen decreased stromal protein synthesis, as measured by counts per min/mg protein, to approximately one third of that found in control patients (control mean, 102,428; tamoxifen-treated mean, 34,111; P less than 0.01). These results support the concept that estrogen has a significant role in the regulation of stromal protein synthesis and the pathophysiology of benign prostatic hypertrophy.