Correlation between circulatory, local prostatic, and intra-prostatic androgen levels

Abstract

Background: Testosterone is converted to the more potent androgen dihydrotestosterone (DHT) in the prostate. DHT and androgen metabolites are inactivated by uridine diphospho (UDP)-glucuronosyl transferase (UGT) enzymes. Here we have studied the influence of the prostate gland on the systemic levels of DHT. Moreover, genetic variation in androgen metabolizing UGT enzymes and the intra-prostatic levels of glucuronidated DHT metabolites were investigated.

Methods: We collected peripheral serum, serum from the local prostatic veins and prostatic tissue from 25 patients undergoing radical prostatectomy. The serum and intra-tissular level of different androgen metabolites were determined by immunological assays and gas chromatography-mass spectrometry (GCMS), respectively.

Results: We found a significant positive correlation between the local prostatic serum DHT levels and (a) prostate weight and (b) circulatory serum levels. There were no correlation between in intra-prostatic hormonal levels and local DHT serum levels. The DHT metabolite 3α-diol-17-glucuronide and 3α-diol-3-glucuronide were significantly associated with UGT2B17 deletion and UGT2B15 Asp85Tyr polymorphisms, respectively.

Conclusion: These results indicate that local prostatic DHT production has an influence on systemic serum DHT levels. Moreover, our results support the evidence that the prostate is the main DHT producer and that UGTs are important in the intra-prostatic regulation of androgens.