C. Guillemette et al., EVIDENCE FOR A ROLE OF GLUCURONOSYLTRANSFERASE IN THE REGULATION OF ANDROGEN ACTION IN THE HUMAN PROSTATIC-CANCER CELL-LINE LNCAP, Journal of steroid biochemistry and molecular biology, 57(3-4), 1996, pp. 225-231
Androgens play an important role in the regulation of cell growth and
specific protein synthesis in hormone-sensitive prostatic cancer. In t
his study, we have investigated the metabolism of androgens in LNCaP c
ells from low passage (LP) and high passage (HP) cultures which were p
reviously shown to possess differential androgen responsiveness. When
treated with dihydrotestosterone (DHT), cells showed the characteristi
c biphasic response of cell proliferation with an ED(50) of 1 nM for b
oth the LP and HP cells, but the maximal proliferative response was di
fferent with values of 2.65- and 4.29-fold over basal for LP and HP ce
lls, respectively. Metabolism studies indicated no difference in 5 alp
ha-reductase activity between LP and HP cells, while 3 alpha-, 3 beta-
and 17 beta-hydroxysteroid dehydrogenase activities were significantl
y higher in LP cultures. The formation of steroid glucuronides (-G), n
amely DHT-G, was higher in LP than in HP cells with values of 2.16 and
1.31 pmol of glucuronides formed/mu g DNA/3 h, respectively. Northern
blot analysis with a UGT2B15 cDNA probe identified two bands correspo
nding to two or more UGT transcripts in both LNCaP cells and more tran
script was observed in LP than in HP cells. Taken together these resul
ts indicate that DHT is deactivated more rapidly in the LP cells, whic
h may explain in part the lower proliferative response to androgens of
LP cells compared with HP cells. Copyright (C) 1996 Published by Else
vier Science Ltd