LHRH and Analogues as Potential Therapy for Benign Prostatic Hyperplasia and Hormone-Dependent Cancers

Abstract

In adult male rats, daily s.c. injections of 0.008–125 μg luteinizing hormone releasing hormone (LHRH) or its analogue (D-Ala⁶, des-Gly-NH₂¹⁰) LHRH ethylamide, led to significant differences in inhibitory effects on testicular function and accessory sex organ weights. The analogue was at least 35 times more potent than LHRH in reducing testicular LH/hCG receptors and 350 times more effective in decreasing plasma testosterone concentrations. In a second study, adult male rats treated with 25–2500 μg LHRH daily for a 3-week period showed 85%-90% decrease in plasma testosterone concentrations. Treatment with 25 or 250 μg LHRH effected a maximal 25% and 40% decrease of the ventral prostate and seminal vesicles, respectively, without affecting the testicular weight, the latter being reduced by 15% with the higher dose of 2500 μg. The LHRH analogue is proposed for the treatment of prostatic and breast cancers while native LHRH could be an effective therapy for benign prostatic hyperplasia.

Key Words:

• LHRH, (D-Ala⁶, des-Gly-NH₂¹⁰) LHRH ethylamide
• Testicular LH/hCG receptors
• Testis
• Prostate
• Testosterone