The GnRH Antagonist Degarelix Directly Inhibits Benign Prostate Hyperplasia Cell Growth
Bibliographic record
Abstract
Gonadotropin-releasing hormone receptors (GnRHR) have been found in extrapituitary tissues, including the prostate, where they might exert a local effect on tissue growth. Degarelix is a GnRHR antagonist approved for use in patients with prostate cancer (PCa) who need androgen deprivation therapy. The slowing of prostate cell growth is a common goal shared by PCa and benign prostate hyperplasia (BPH) patients, and the effect of degarelix on BPH cells has not yet been investigated. We wanted to evaluate the direct effect of degarelix on human BPH primary cell growth. Gene expression studies performed with BPH (n=11), stage 0 (n=15), and PCa (n=65) human specimens demonstrated the presence of GNRHR1 and GNRHR2 and their respective endogenous peptide ligands. BPH-isolated epithelial and stromal cells were either cultured alone or co-cultured (1:4 or 4:1 ratio of epithelial to stromal cells) and subsequently treated with increasing concentrations of degarelix. Degarelix treatment induced a decrease in cell viability and cell proliferation rates, which occurred in parallel to an increase in apoptosis. Both epithelial and stromal BPH cells are sensitive to degarelix treatment and, interestingly, degarelix is also effective when the cells were growing in a co-culture microenvironment. In contrast to degarelix, the GnRHR agonists, leuprolide and goserelin, exerted no effect on the viability of BPH epithelial or stromal cells. In conclusion, (i) prostate tissues express GNRHR and are a potential target for degarelix; and (ii) degarelix directly inhibits BPH cell growth through a decrease in cell proliferation and an increase in apoptosis. Supporting information for this article is available online at http://www.thieme-connect.de/products.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".