Receptors for luteinizing hormone-releasing hormone (LHRH) in benign prostatic hyperplasia (BPH) as potential molecular targets for therapy with LHRH antagonist cetrorelix

• Published in: The Prostate 2011-04, Vol.71 (5), p.445-452
• Main Authors: Rozsa, Bernadett, Nadji, Mehrdad, Schally, Andrew V., Dezso, Balazs, Flasko, Tibor, Toth, Gyorgy, Mile, Melinda, Block, Norman L., Halmos, Gabor
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Binding, Competitive; Gonadotropin-Releasing Hormone - analogs & derivatives; Gonadotropin-Releasing Hormone - antagonists & inhibitors; Gonadotropin-Releasing Hormone - metabolism; Gonadotropin-Releasing Hormone - pharmacology; Hormone Antagonists - pharmacology; human benign prostatic hyperplasia; Humans; Immunohistochemistry; LHRH antagonist; luteinizing hormone-releasing hormone (LHRH) receptors; Male; Middle Aged; Molecular Targeted Therapy - methods; Prostatic Hyperplasia - drug therapy; Prostatic Hyperplasia - genetics; Prostatic Hyperplasia - metabolism; Radioligand Assay; Receptors, LHRH - antagonists & inhibitors; Receptors, LHRH - biosynthesis; Receptors, LHRH - genetics; Receptors, LHRH - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - biosynthesis; RNA, Messenger - genetics
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/pros.21258

BACKGROUND The majority of men will develop symptoms of benign prostatic hyperplasia (BPH) after 70 years of age. Various studies indicate that antagonists of LHRH, such as cetrorelix, exert direct inhibitory effects on BPH mediated by specific LHRH receptors. Our aim was to investigate the mRNA for LHRH and LHRH receptors and the expression of LHRH receptors in specimens of human BPH. METHODS The expression of mRNA for LHRH (n = 35) and LHRH receptors (n = 55) was investigated by RT‐PCR in surgical specimens of BPH, using specific primers. The characteristics of binding sites for LHRH on 20 samples were determined by ligand competition assays. The LHRH receptor expression was also examined in 64 BPH specimens by immunohistochemistry. RESULTS PCR products for LHRH were found in 18 of 35 (51%) BPH tissues and mRNA for LHRH receptors was detected in 39 of 55 (71%) BPH specimens. Eighteen of 20 (90%) samples showed a single class of high affinity binding sites for [D‐Trp6]LHRH with a mean Kd of 4.04 nM and a mean Bmax of 527.6 fmol/mg membrane protein. LHRH antagonist cetrorelix showed high affinity binding to LHRH receptors in BPH. Positive immunohistochemical reaction for LHRH receptors was present in 42 of 64 (67%) BPH specimens. CONCLUSION A high incidence of LHRH receptors in BPH supports the use of LHRH antagonists such as cetrorelix, for treatment of patients with lower urinary tract symptoms from BPH. Prostate 77:445–452, 2011. © 2010 Wiley‐Liss, Inc.