Acute effects of testicular and adrenal cortical blockade on protein synthesis and dihydrotestosterone content of human prostate tissue.

Abstract

To examine the relationship between whole prostatic dihydrotestosterone (DHT) concentrations and epithelial and stromal protein synthesis, patients awaiting surgery for benign prostatic hypertrophy were given medication to reduce circulating and tissue androgen levels for comparison to levels in untreated patients. The medications, either megestrol acetate, a progestational antiandrogen, or megestrol acetate plus dexamethasone, were given for 1 week before surgery. Aliquots of prostate tissue obtained at surgery were assayed for DHT. The remainder of the tissue was separated into stromal and epithelial cells using enzymatic separation; the incorporation of both [3H] proline into stromal protein and [3H]leucine into epithelial cell protein was then measured. Over a wide range of tissue DHT concentrations, DHT correlated significantly with [3H]proline incorporation into stromal protein (r = 0.58). Likewise, epithelial cell incorporation of [3H]leucine into protein correlated significantly with tissue DHT concentrations, with a r value of 0.79. In the case of stromal cells, no additional effects of dexamethasone given with megestrol acetate were found on stromal protein synthesis. Epithelial cell [3H]leucine incorporation into protein was paradoxically enhanced by dexamethasone plus megestrol acetate compared to the latter alone, despite the fact that tissue DHT and circulating adrenal androgens, dehydroepiandrosterone sulfate and delta 4-androstenedione, were not significantly different from values obtained after treatment with megestrol acetate alone. These studies support the conclusion that there is a dominant role of DHT in regulating protein synthesis in both prostatic epithelial and stromal cells. Dexamethasone appears to have a growth-stimulating effect on prostatic epithelial cells.