HUMAN PROSTATIC-CARCINOMA CELL-LINE LNCAP DEGRADES LUTEINIZING-HORMONE-RELEASING HORMONE

Recent evidence suggests a direct antiproliferative effect of LHRH agonists on the prostatic carcinoma cell line LNCaP. In the present study the possible presence of a LHRH degrading activity (LHRH-DA) in soluble fractions of LNCaP cell homogenates has been investigated. The results obtained show that an LHRH-DA is present in the soluble fraction of LNCaP cells with apparent Km and Vmax values of 31.6 mu M and 4.5 pmol/min/mu g protein respectively. The degradation pattern of LHRH is characterized by two major initial degradation products identified as LHRH 1-5 and LHRH 1-6 fragments. The degradation of the tracer [pGlu-H-3]LHRH, used as a substrate, is inhibited by synthetic unlabelled LHRH (IC50 7.9 mu M) and by several LHRH agonists with different kinetics and potencies; the LHRH agonist [DSer-(tBu)(6),Gly(10)-Aza]LHRH was the most potent blocker of LHRH-DA present in LNCaP cells; this enzymatic activity is also inhibited in a dose dependent manner by somatostatin, TRH, bacitracin and dithiothreitol. The LHRH-DA present in the soluble fraction of LNCaP cells does not seem to be modified by the deprivation of steroids from the culture medium, In conclusion, the presence in LNCaP cells of a soluble peptidase able to degrade LHRH might reinforce the possibility that the prostate is a target for the action of LHRH and of LHRH analogs.