Androgen deprivation promotes intratumoral synthesis of dihydrotestosterone from androgen metabolites in prostate cancer

作者：Ishizaki Fumio; Nishiyama Tsutomu^*; Kawasaki Takashi; Miyashiro Yoshimichi; Hara Noboru; Takizawa Itsuhiro; Naito Makoto; Takahashi Kota

来源：Scientific Reports, 2013, 3(1): 1528.

DOI：10.1038/srep01528

Intratumoral synthesis of dihydrotestosterone(DHT) from precursors cannot completely explain the castration resistance of prostate cancer. We showed that DHT was intratumorally synthesized from the inactive androgen metabolites 5 alpha-androstane-3 alpha/beta, 17 beta-diol(3 alpha/beta-diol) in prostate cancer cells via different pathways in a concentration-dependent manner. Additionally, long-term culture in androgen-deprived media increased transcriptomic expression of 17 beta-hydroxysteroid dehydrogenase type 6(HSD17B6), a key enzyme of oxidative 3 alpha-HSD that catalyzes the conversion of 3 alpha-diol to DHT in prostate cancer cells. Correspondingly, the score for HSD17B6 in tissues of 42 prostate cancer patients undergoing androgen deprivation therapy(ADT) was about 2-fold higher than that in tissues of 100 untreated individuals. In men receiving ADT, patients showing biochemical progression had a higher HSD17B6 score than those without progression. These results suggested that 3 alpha/beta-diol also represent potential precursors of DHT, and the back conversion of DHT from androgen derivatives can be a promising target for combination hormone therapy.

• 出版日期2013-3-25