ANDROGEN REGULATION OF THE MESSENGER-RNA ENCODING DIAZEPAM-BINDING INHIBITOR ACYL-COA-BINDING PROTEIN IN THE HUMAN PROSTATIC ADENOCARCINOMACELL-LINE LNCAP

To study the mechanisms by which androgens intervene in the regulation of growth and differentiation of human prostatic epithelial cells, cD NA clones encoding putative prostate-secreted proteins were characteri zed and tested as potential markers for androgen action. One of the is olated cDNAs expressed diazepam-binding inhibitor/acyl-CoA-binding pro tein (DBI/ACBP), suggesting that this polypeptide, that has been impli cated in a large number of biochemical processes, is expressed and sec reted by prostate cells. As demonstrated by Northern blot analysis, th e mRNA encoding DBI/ACBP was expressed in prostate tissue and in the t hree human prostatic adenocarcinoma cell lines tested: LNCaP, PC-3 and DU-145. In androgen-sensitive LNCaP cells, the synthetic androgen R18 81 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 af ter 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. A ndrogen stimulation of DBI/ACBP mRNA levels was abolished in the prese nce 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 p rostate-specific antigen (PSA), suggesting that different mechanisms a re involved in the androgen regulation of these two genes. Although fu rther experiments are required to confirm that DBI/ACBP is secreted by prostatic epithelial cells, these data demonstrate that the mRNA enco ding DBI/ACBP is expressed in prostate cells and is affected by androg ens in androgen-responsive LNCaP cells.