To study the mechanisms by which
androgens intervene in the regulation of growth and differentiation of human prostatic epithelial cells,
cDNA clones encoding putative prostate-secreted
proteins were characterized and tested as potential markers for
androgen action. One of the isolated cDNAs expressed
diazepam-binding inhibitor/
acyl-CoA-binding protein (
DBI/ACBP), suggesting that this
polypeptide, that has been implicated in a large number of biochemical processes, is expressed and secreted by prostate cells. As demonstrated by Northern blot analysis, the
mRNA encoding
DBI/ACBP was expressed in prostate tissue and in the three human prostatic
adenocarcinoma cell lines tested: LNCaP, PC-3 and DU-145. In
androgen-sensitive LNCaP cells, the
synthetic androgen R1881 stimulated the
DBI/ACBP steady state
mRNA levels with half maximal effects at a concentration of 0.2 nM. Increases were a maximal 12 h after addition of the synthetic
hormone.
DBI/ACBP
mRNA levels could also be stimulated by the
synthetic androgen mibolerone and by the natural
androgens testosterone and
dihydrotestosterone. In agreement with the altered
steroid specificity of the
androgen receptor in LNCaP cells,
estradiol and
progesterone also exerted a stimulatory effect.
Cortisol and the synthetic
glucocorticoid dexamethasone were without effect.
Androgen stimulation of
DBI/ACBP
mRNA levels was abolished in the presence of the
protein synthesis inhibitor cycloheximide, implying a role for labile or
androgen-induced
proteins in this
androgen stimulation. This is in contrast to the
androgen stimulation of the
mRNA encoding
prostate-specific antigen (PSA), suggesting that different mechanisms are involved in the
androgen regulation of these two genes. Although further experiments are required to confirm that
DBI/ACBP is secreted by prostatic epithelial cells, these data demonstrate that the
mRNA encoding
DBI/ACBP is expressed in prostate cells and is affected by
androgens in
androgen-responsive LNCaP cells.