The GnRH Antagonist Degarelix Directly Inhibits Benign Prostate Hyperplasia Cell Growth

Area of Science:

• Endocrinology
• Urology
• Cell Biology

Background:

• Gonadotropin-releasing hormone receptors (GnRHR) are present in extrapituitary tissues, including the prostate, potentially influencing local tissue growth.
• Degarelix, a GnRHR antagonist, is approved for prostate cancer (PCa) treatment, but its effect on benign prostate hyperplasia (BPH) cells is uninvestigated.
• Both PCa and BPH involve prostate cell growth, making GnRHR antagonists a potential therapeutic avenue for BPH.

Purpose of the Study:

• To investigate the direct effect of degarelix on the growth of primary human benign prostate hyperplasia (BPH) cells.
• To determine if BPH cells express GnRHRs and their endogenous ligands.
• To compare the effects of degarelix with GnRHR agonists on BPH cell viability.

Main Methods:

• Gene expression analysis of GnRHR1, GnRHR2, and their ligands in human BPH, normal, and PCa prostate tissues.
• Culture of isolated BPH epithelial and stromal cells, both alone and co-cultured.
• Treatment of BPH cells with varying concentrations of degarelix and assessment of cell viability, proliferation, and apoptosis.
• Comparison of degarelix effects with GnRHR agonists (leuprolide, goserelin).

Main Results:

• Human prostate tissues (BPH, normal, PCa) express GnRHR1, GnRHR2, and their ligands.
• Degarelix treatment significantly decreased BPH epithelial and stromal cell viability and proliferation.
• Degarelix treatment increased apoptosis in both BPH cell types, irrespective of co-culture conditions.
• GnRHR agonists leuprolide and goserelin did not affect BPH cell viability.

Conclusions:

• Prostate tissues express GnRHRs, identifying them as a potential therapeutic target for degarelix.
• Degarelix directly inhibits BPH cell growth by decreasing proliferation and increasing apoptosis.
• Degarelix demonstrates efficacy on BPH cells in both isolated and co-cultured environments, unlike GnRHR agonists.