Adrenal steroids in human prostatic cancer cell lines

Adrenal androgens function as an androgen source within prostate and androg en target tissue. This study compares the ability of three human prostatic cancer cell lines to metabolize the adrenal andro gens, dehydroepiandroster one (DHEA), and androstenedione under living culture conditions. Androgen-i ndependent cell lines PC-3 and DU145 and androgen-dependent cell line LNCaP were investigated. The effect of glucuronide and sulfate conjugates was al so investigated. Then was a strong tendency in PC-3 or DU145 to convert and rostenedione to DHEA or DHEA-S reservoir. On the other hand, LNCaP was capa ble of converting DHEA into androstenedione and subsequently into dihydrote stosterone (DHT). Moreover, androgens were converted into a glucuronide con jugate in LNCaP. but not in PC-3 or DU145. As a result, the metabolism of t he adrenal precursor shifted to androgen formation in LNCaP. This could be confirmed by means of reverse transcription-PCR of uridine diphosphoglucuro nosyl-transferase (UGT) 2B15. Kinetic properties of UGT activity in LNCaP r evealed DHT to be a better substrate than testosterone. In conclusion, the findings show that the adrenal precursor pool has the potential to contribu te to the regulation of prostatic cells. Moreover, the presence of UGT acti vities in LNCaP may have a regulatory effect on the active androgen level i n the intracellular environment.