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

Abstract

Purpose: Agonistic analogs of luteinizing hormone-releasing hormone (LHRH) are widely used for therapy of advanced prostate cancer based upon their ability 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 adenocarcinomas and benign prostatic tissue.

Materials and methods: In vitro ligand competition assays as well as reverse transcriptase polymerase chain reaction (RT-PCR) were performed to investigate the expression of receptors for LHRH in surgical specimens of human prostate cancers and benign prostatic tissue.

Results: Sixty-nine of 80 (86%) cancers exhibited specific, medium to high-affinity binding for [D-Trp6]LHRH with a dissociation constant (Kd) of 6.55+/-0.4 nM and a maximal binding capacity (Bmax) of 483.6+/-25.4 fmol./mg. membrane protein. Two prostate cancer patients who were treated with the LHRH agonist goserelin prior to prostatectomy did not show tumor LHRH receptors. The expression of mRNA for LHRH receptors was observed in 19 of 22 (86%) prostate cancers. Benign prostatic tissue also displayed LHRH receptor gene expression, but exhibited lower Bmax value. There was a negative correlation (p <0.001) between LHRH receptor binding capacity and cancer grade (Gleason score); higher Gleason scores were associated with significantly lower binding capacity but 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 therapy of this malignancy based on LHRH analogs.