The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2018

Inherent prostate contractility is significantly increased in men with benign prostatic hyperplasia and is regulated by the peptide hormone oxytocin (#50)

Sophie N Lee 1 , Jenna Kraska 1 , Melissa Papagiris 1 , Ralf Middendorff 2 , Stuart J Ellem 1 , Michael Whittaker 3 , Gail P Risbridger 1 , Betty Exintaris 3
  1. Monash University, Clayton, VIC, Australia
  2. Institute of Anatomy and Cell Biology, Justus-Liebig University , Giessen, Hesse, Germany
  3. Drug Discovery Biology, Monash University, Parkville, VIC, Australia

Androgens are essential for prostate growth and development of the prostate gland but aberrant signalling significantly contributes to both malignant (prostate cancer) and benign (Benign Prostatic Hyperplasia (BPH)) disease in adult men. BPH affects 80% of men by the age of 80 and its aetiology beyond the involvement of androgens is poorly understood. There are two components; a static component (driven by androgens increasing stromal proliferation) and a dynamic component (changing contractility of the prostate). Based on previous literature, the objective of this study was to define the role and action of locally synthesised Oxytocin on endogenous (myogenic) contractility.

Tension recordings of myogenic tone were obtained from primary human prostate tissue collected from a clinically diverse cohort of men. Preparations were incubated with increasing concentrations of Oxytocin in the presence or absence of Atosiban (300nM; Oxytocin Receptor (OXTR) antagonist). Unstimulated preparations were incubated with Atosiban (300nM) alone.

The frequency of myogenic contractions was significantly (p < 0.05) greater in specimens from men with clinically diagnosed BPH compared to age- or volume-matched controls. Application of exogenous Oxytocin significantly (p < 0.05) increased the frequency of myogenic contractions in a dose dependent manner and was attenuated in the presence of Atosiban. Application of Atosiban on unstimulated sections significantly (p < 0.05) reduced the frequency of myogenic contractions by 34.9 ± 7.8%.

Utilizing our unique model of human prostate contractility, we have established that myogenic tone is significantly upregulated in men with clinically diagnosed BPH. Exogenous Oxytocin, acting through the OXTR, amplified the frequency of myogenic contractions. Antagonism of the OXTR in unstimulated tissue attenuated the frequency of contractions, suggesting endogenous production of Oxytocin contributes to myogenic tone. Collectively, our data indicates that Oxytocin is a regulator of myogenic tone and should be investigated further as a potential pharmacotherapy for BPH.