Role of oxytocin in the contractilityof the male reproductive tract: implications for the treatment of benign prostatic hyperplasia
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Beschreibung
The adrenergic pathway is said to transmit the main contractile effects in the male reproductive tract. However, the underlying mechanisms and the interplay of the different components involved is unclear. The first line of medical treatment options today for patients with benign prostatic hyperplasia (BPH) targets the α1-adrenoreceptor. Since the α1-adrenoreceptor is expressed throughout the male reproductive tract and is heavily involved in mediating the ejaculatory process, BPH patients often complain about off-target effects such as ejaculatory disorders, especially when using tamsulosin. Other than from complications with adrenergic blockers, ejaculatory disorders are quite common as well. Finding other agents that are involved in transmitting contractile effects in the male reproductive tract, such as oxytocin, would further our basic understanding of male reproduction and open up new strategies in the treatment of ejaculatory disorders and BPH.
To clarify if oxytocin-based medications could be an alternative to existing treatment options for BPH as well as ejaculatory disorders, we used live imaging to investigate the effect of oxytocin as a contractile agent in the prostate and the epididymis in both rat and human tissue. At the same time, we wanted to provide further insight into the differences of prostatic ducts compared to glands. This had originally been observed in the rat and we sought to clarify the structure of the prostatic duct system in the human prostate, where it has not been fully described to date.
We demonstrated that oxytocin had an increasing effect on the contractility of the human prostate but not on the rat prostate. Furthermore, we showed that the effect of oxytocin on the contractility of the epididymis varied depending on the segment investigated. We found that only the very last segment of the adult epididymis (S19 in the rat and S9 in the human) showed a uniquely strong response, indicative of its function as the driving force in expelling the sperm from epididymal storage during the ejaculatory process. This strong response in S19 of the adult rat epididymis was equally induced by either oxytocin or norepinephrine and absent in neonatal tissue. Furthermore, the response to oxytocin was concentration dependent and mainly mediated through the oxytocin receptor. Our results also showed that the oxytocin pathway signalling was completely independent from the adrenergic pathway, and vice versa, in the last segment of the epididymis.
Taken together this leads us to conclude that using oxytocin-based medication could be an effective and new approach in treating BPH and ejaculatory disorders, especially by supporting ejaculation. In addition, we propose that S19 is an advantageous model to test newly developed molecules targeting either the oxytocin or the adrenergic pathway. To reach this conclusion we also created a new method to analyze contractions in live imaging data.
We also gained first insights into the human prostatic duct system structure indicating a branching system predominantly draining into the urethra on the dorsal aspect, probably on the colliculus seminalis. We suggest that the combination of micro-CT imaging and then embedding these scanned samples for a histological work-up to be a valuable tool in localizing and investigating previously unknown structures (such as the prostatic ducts) accurately. We also obtained preliminary evidence in our prostate micro-CT scans for a specific organization of the tissue surrounding the prostatic ducts in the human prostate, which could also implicate a specific function and possibly a differing contractile pattern.
Autor*in
Beatrix Stadler