Adrenal steroids in human prostatic cancer cell lines.
Adrenal androgens function as an androgen source within prostate and androgen target tissue. This study compares the ability of three human prostatic cancer cell lines to metabolize the adrenal androgens, dehydroepiandrosterone (DHEA), and androstenedione under living culture conditions. Androgen-independent cell lines PC-3 and DU145 and androgen-dependent cell line LNCaP were investigated. The effect of glucuronide and sulfate conjugates was also investigated. There was a strong tendency in PC-3 or DU145 to convert androstenedione to DHEA or DHEA-S reservoir. On the other hand, LNCaP was capable of converting DHEA into androstenedione and subsequently into dihydrotestosterone (DHT). Moreover, androgens were converted into a glucuronide conjugate in LNCaP, but not in PC-3 or DU145. As a result, the metabolism of the adrenal precursor shifted to androgen formation in LNCaP. This could be confirmed by means of reverse transcription-PCR of uridine diphosphoglucuronosyl-transferase (UGT) 2B15. Kinetic properties of UGT activity in LNCaP revealed DHT to be a better substrate than testosterone. In conclusion, the findings show that the adrenal precursor pool has the potential to contribute to the regulation of prostatic cells. Moreover, the presence of UGT activities in LNCaP may have a regulatory effect on the active androgen level in the intracellular environment.
Koh
E
E
Department of Urology, School of Medicine, Kanazawa University, Japan. kohei@med.kanazawa-u.ac.jp
Kanaya
J
J
Namiki
M
M
D000735:Androstenedione / Q000378:metabolism*; D002855:Chromatography, Thin Layer; D017931:DNA Primers / Q000737:chemistry; D003687:Dehydroepiandrosterone / Q000378:metabolism*; D005965:Glucuronates; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured / Q000378:metabolism
D017931:DNA Primers; D005965:Glucuronates; D020033:Protein Isoforms; D012333:RNA, Messenger; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D014453:Glucuronosyltransferase