Relationship between human prostatic epithelial cell protein synthesis and tissue dihydrotestosterone level.
To evaluate the role of small amounts of prostatic tissue dihydrotestosterone (DHT) as a stimulus to epithelial cell protein synthesis, we studied tissue from 27 patients given various androgen-blocking drugs for 1 week before transurethral resection of the prostate (TURP) and measured epithelial protein synthesis and DHT levels in the tissue specimens. Test drugs before TURP included megestrol acetate 160 mg per day, with and without Tamoxifen 40 mg per day, or ketoconazole 1200 mg per day. The tissue was processed immediately and epithelial cells separated by digestion of tissue with 0.5% collagenase. After separation, epithelial cells were labelled with either 3H-leucine or L-35S-methionine. The DHT level was measured in whole prostatic tissue. Megestrol acetate alone and with tamoxifen significantly decreased both the incorporation of 3H-leucine into protein and the tissue concentration of DHT; megestrol acetate plus ketoconazole significantly decreased L-35S-methionine incorporation into protein and the DHT level. When the data correlating DHT with protein synthesis using both labelling techniques were combined, the curves were parallel and a strong correlation was noted between DHT and protein synthesis over a wide range of values (P less than 0.001). These results suggest that in hormone-dependent prostatic cancer even small amounts of prostatic DHT such as may occur from adrenal androgens following castration may significantly stimulate protein synthesis of the tumour epithelial cells.
Geller
J
J
Research Facility-Medical Education Department, Mercy Hospital and Medical Center, San Diego, California 92103-2180.
Liu
J
J
Albert
J
J
Fay
W
W
Berry
C C
CC
Weis
P
P
D000368:Aged; D013196:Dihydrotestosterone / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D007654:Ketoconazole / Q000494:pharmacology; D008297:Male; D008535:Megestrol / Q000031:analogs & derivatives / Q000494:pharmacology; D019290:Megestrol Acetate; D011467:Prostate / Q000187:drug effects / Q000378:metabolism*; D014176:Protein Biosynthesis; D013629:Tamoxifen / Q000494:pharmacology
D013196:Dihydrotestosterone; D013629:Tamoxifen; D008535:Megestrol; D007654:Ketoconazole; D019290:Megestrol Acetate