Mechanisms of synergism between antagonists of growth hormone-releasing hormone and antagonists of luteinizing hormone-releasing hormone in shrinking experimental benign prostatic hyperplasia.
Rick. Ferenc G FG; Schally. Andrew V AV; Block. Norman L NL; Abi-Chaker. Andrew A; Krishan. Awtar A; Szalontay. Luca L
Key Findings
- Combined GHRH antagonist (JMR‑132) and LHRH antagonist (cetrorelix) reduced rat prostate weight by ~29.5%.
- In BPH‑1 prostate epithelial cells, the combo inhibited growth by 57.4% and caused cell‑cycle arrest in S‑phase.
- Normal stromal prostate cells (WPMY‑1) showed a smaller growth inhibition (46%), indicating some selectivity.
- Over 40 genes linked to growth factors, inflammation, and signaling were significantly altered by the treatment.
Practical Outcomes
- For DIY health enthusiasts, the findings are not yet ready for personal use: the study uses drug antagonists (which block hormone signals) rather than the more common sermorelin agonist, and all data are from rats and cell lines. Until human trials confirm safety and efficacy, there’s no actionable protocol to adopt for prostate health.
Summary
In rats, blocking both growth‑hormone‑releasing hormone (GHRH) and luteinizing‑hormone‑releasing hormone (LHRH) shrank the prostate by about 30%. In human prostate cell cultures, the two blockers together stopped cancer‑like cells from growing, mainly by trapping them in the DNA‑synthesis (S) phase. Normal prostate stromal cells were less affected. The study suggests this drug combo could be a new way to treat benign prostate enlargement, but it’s still early‑stage animal work.
Abstract
Benign prostatic hyperplasia (BPH) affects aging men. Combined therapy with antagonists of growth hormone-releasing hormone (GHRH) and of luteinizing hormone-releasing hormone (LHRH or GnRH) induces prostate shrinkage in rat models. We investigated the mechanisms of action of this combination on cell cycle traverse and expression of prostatic genes. Effects of GHRH antagonist, JMR-132 (40 µg/day), the LHRH antagonist, cetrorelix (0.625 mg/kg), and their combination were evaluated on testosterone-induced benign prostatic hyperplasia in male Wistar rats. Influence of JMR-132, cetrorelix, and their combinations on cell viability was assessed by MTS assay in BPH-1 human prostate epithelial cells and WPMY-1 normal prostate stromal cells. Cell cycle was analyzed by laser flow cytometry. Real-time PCR arrays were performed. The combination of antagonists caused marked shrinkage of rat prostate (29.5%). In vitro, JMR-132 plus cetrorelix (both 5µM) produced synergistic (57.4%) inhibition of growth of BPH-1 cells, but a lesser inhibition (46%) of WPMY-1 cells. Co-treatment of with JMR-132 plus cetrorelix induced a significant increase of BPH-1 cells blocked in S-phase plus cells with lower G0 /G1 and G2 /M DNA content. Significant changes in expression of >40 gene transcripts related to growth factors, inflammatory cytokines, and signal transduction were identified. GHRH antagonist and LHRH antagonist combination potentiates rat prostate weight reduction and synergistically inhibits of growth of BPH-1 leading to cell cycle arrest in S-phase. These effects were lesser in normal stromal prostate cell line, WPMY-1. Our findings suggest that GHRH antagonists could be useful for BPH therapy, possibly in combination with LHRH antagonists.
Study Information
pubmed
2012
2012-12-31T00:00:00.000Z
10.1002/pros.22633
30
65