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Horm Metab Res 2015; 47(12): 925-931
DOI: 10.1055/s-0035-1555899
Endocrine Research
© Georg Thieme Verlag KG Stuttgart · New York

The GnRH Antagonist Degarelix Directly Inhibits Benign Prostate Hyperplasia Cell Growth

M. Sakai
1   The Research Institute of the McGill University Health Center, McGill University, Montréal, Québec, Canada
2   Department of Medicine, McGill University, Montréal, Québec, Canada
,
M. Elhilali
1   The Research Institute of the McGill University Health Center, McGill University, Montréal, Québec, Canada
3   Department of Surgery, McGill University, Montréal, Québec, Canada
,
V. Papadopoulos
1   The Research Institute of the McGill University Health Center, McGill University, Montréal, Québec, Canada
2   Department of Medicine, McGill University, Montréal, Québec, Canada
4   Department of Biochemistry, McGill University, Montréal, Québec, Canada
5   Department of Pharmacology & Therapeutics, McGill University, Montréal, Québec, Canada
› Author Affiliations
Further Information

Publication History

received 28 November 2014

accepted 25 June 2015

Publication Date:
21 July 2015 (online)

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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

Key words

gonadotropin-releasing hormone - primary cells - co-culture - epithelial - stromal - endocrinology

Supporting Information

 

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