High incidence of receptors for luteinizing hormone-releasing hormone (LHRH) and LHRH receptor gene expression in human prostate cancers

Purpose: Agonistic analogs of luteinizing hormone-releasing hormone (LHRH) are widely used for therapy of advanced prostate cancer based upon their ab ility to suppress testosterone secretion in patients. Various studies also indicate that LHRH analogs might have direct inhibitory effects on prostate tumors mediated by specific LHRH receptors. In this study we investigated the presence and characteristics of receptors for LHRH and their messenger (m) ribonucleic acid (RNA) expression in specimens of human prostate adenoc arcinomas and benign prostatic tissue. Materials and Methods: In vitro ligand competition assays as well as revers e transcriptase polymerase chain reaction (RT-PCR) were performed to invest igate the expression of receptors for LHRH in surgical specimens of human p rostate cancers and benign prostatic tissue. Results: Sixty-nine of 80 (86% ) cancers exhibited specific, medium to high-affinity binding for [D-Trp(6) ]LHRH with a dissociation constant (K-d) of 6.55 +/- 0.4 nM and a maximal b inding capacity (B-max) of 483.6 +/- 25.4 fmol./mg. membrane protein. Two p rostate cancer patients who were treated with the LHRH agonist goserelin pr ior to prostatectomy did not show tumor LHRH receptors. The expression of m RNA for LHRH receptors was observed in 19 of 22 (86%) prostate cancers. Ben ign prostatic tissue also displayed LHRH receptor gene expression, but exhi bited lower B-max value. There was a negative correlation (p < 0.001) betwe en LHRH receptor binding capacity and cancer grade (Gleason score); higher Gleason scores were associated with significantly lower binding capacity bu t an increased binding affinity. Conclusions: The expression of specific receptor proteins for LHRH in human prostate cancer provides a rationale for the improvement in methods for th erapy of this malignancy based on LHRH analogs.