Relationship between human prostatic epithelial cell protein synthesis and tissue dihydrotestosterone level.

Area of Science:

• Endocrinology
• Oncology
• Molecular Biology

Background:

• Prostatic dihydrotestosterone (DHT) is a key androgen.
• DHT's role in stimulating epithelial cell protein synthesis requires further elucidation, especially in hormone-dependent prostate cancer.
• Understanding DHT's influence is critical for developing effective cancer therapies.

Purpose of the Study:

• To evaluate the role of prostatic tissue dihydrotestosterone (DHT) in stimulating epithelial cell protein synthesis.
• To investigate the impact of androgen-blocking drugs on DHT levels and protein synthesis in prostate tissue.
• To establish the correlation between DHT levels and epithelial protein synthesis.

Main Methods:

• Studied prostate tissue from 27 patients undergoing transurethral resection of the prostate (TURP) after 1 week of treatment with megestrol acetate, tamoxifen, or ketoconazole.
• Separated epithelial cells using collagenase digestion and labeled them with 3H-leucine or L-35S-methionine to measure protein synthesis.
• Measured DHT levels in whole prostatic tissue specimens.

Main Results:

• Megestrol acetate (alone or with tamoxifen) significantly decreased both 3H-leucine incorporation and DHT levels.
• Megestrol acetate plus ketoconazole significantly decreased L-35S-methionine incorporation and DHT levels.
• A strong positive correlation (P < 0.001) was observed between DHT levels and epithelial protein synthesis across a wide range of values.

Conclusions:

• Prostatic DHT, even in small amounts, significantly stimulates protein synthesis in hormone-dependent prostate cancer epithelial cells.
• These findings suggest that residual DHT from adrenal androgens post-castration can drive tumor cell protein synthesis.
• Targeting even low levels of DHT may be a viable strategy for managing hormone-dependent prostate cancer.