With increasing life expectancy, benign prostatic hyperplasia (BPH) consequently affects more ageing men, illustrating the urgent need for advancements in BPH therapy. One emerging possibility may be the use of oxytocin antagonists to relax smooth muscle cells in the prostate, similar to the currently used (although often associated with side effects) α1-adrenoceptor blockers.
For the first time we used live-imaging, combined with a novel image analysis method, to investigate the multidirectional contractions of the human prostate and determine their changes in response to oxytocin and the oxytocin antagonists atosiban and cligosiban. Human prostate samples were obtained and compared from patients undergoing prostatectomy due to prostate cancer as well as from patients with transurethral resection of prostate tissue due to severe BPH.
The two cohorts of tissue samples showed spontaneous multidirectional contractions, which significantly increased after the addition of oxytocin. Different to atosiban, which showed ambiguous effects of short duration, only long-acting cligosiban reliably prevented, as well as counteracted, any contractile oxytocin effect. Furthermore, cligosiban visibly reduced not only oxytocin-induced contractions, but also showed intrinsic activity to relax prostatic tissue.
Thus, the oxytocin antagonist cligosiban could be an interesting candidate in the search for novel BPH treatment options.
British journal of pharmacology. 2024 Apr 27 [Epub ahead of print]
Beatrix Bester, Kristina Koslowa, Ann-Catherine Gronau, Andrea Mietens, Cameron Nowell, Michael R Whittaker, Adrian Pilatz, Florian Wagenlehner, Betty Exintaris, Ralf Middendorff
Institute of Anatomy and Cell Biology, Justus-Liebig-University, Giessen, Germany., Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Melbourne, Victoria, Australia., Drug Discovery Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Melbourne, Victoria, Australia., Department of Urology, Pediatric Urology, and Andrology, Justus-Liebig-University, Giessen, Germany.