Estrogen reduces smooth muscle contractility in the human prostate gland

Lee S1, Kraska J1, Papargiris M1, Teng L1, Niranjan B1, Ryan A2, Frydenberg M1, Lawrentschuk N3, Middendorff R4, Ellem S1, Risbridger G1, Exintaris B1

Research Type

Pure and Applied Science / Translational

Abstract Category

Male Lower Urinary Tract Symptoms (LUTS) / Voiding Dysfunction

Abstract 291
On Demand Male Lower Urinary Tract Symptoms (LUTS) / Voiding Dysfunction
Scientific Open Discussion Session 22
On-Demand
Benign Prostatic Hyperplasia (BPH) Physiology Basic Science Pharmacology Male
1. Monash University, 2. Tissue Path, 3. Melbourne University, 4. Justus-Liebig-University Giessen
Presenter
B

Betty Exintaris

Links

Abstract

Hypothesis / aims of study
Both static and dynamic processes play a role in the pathophysiology of bladder outlet obstruction (BOO) associated with benign prostatic hyperplasia (BPH). The static component (cellular proliferation) is hormonally regulated by androgen and estrogen receptor signalling. In contrast, the hormonal regulation of the dynamic smooth muscle tone is poorly understood, yet the dynamic component is a key target of several BPH pharmacotherapies including alpha 1 antagonists and phosphodiesterase (5) inhibitors.  In this study, our aim was to investigate the effects of estrogen on human prostatic smooth muscle contractility.  We hypothesised that changes in smooth muscle tone are mediated by non-genomic estrogen signalling through the G Protein Estrogen Receptor (GPER).
Study design, materials and methods
Human prostate tissue was collected from the transition zone (TZ) of a cohort of men undergoing radical prostatectomy, and conventional tension recordings were used to assess spontaneous contractility of the tissue following treatment with the GPER specific agonist (G1) and compared to 17β-estradiol (E2).   The key parameters assessed were basal tension (mN), adjusted amplitude (N/g) and frequency. Data is expressed as the mean ± SEM.
Results
Non-malignant TZ specimens were obtained from a cohort of men with an average age of 64±3.14 years. Application of 100nM 17β-estradiol (E2) significantly reduced the basal tension (Δ-6.16±2.07%) and adjusted amplitude (Δ-29.57±7.52%) of the spontaneous contractions of the prostate within 10 minutes (p<0.05, n=6).   There was a notable interpatient variability in the reduction of parameters in response to 17β-estradiol.   Regression analysis determined that age was strongly negatively correlated (R2 = 0.633) with the percentage decrease of the adjusted amplitude of contractions, indicating that older men had a greater reduction in the adjusted amplitude of spontaneous contractions in response to E2.
The rapid, significant decrease in spontaneous contractile parameters by 100nM E2 was replicated in patient matched specimens by the G Protein Estrogen Receptor specific agonist, G1, with no significant difference in efficacy observed between 100nM E2 and 100nM G1 (Paired two way ANOVA with Dunnets post hoc test, n = 5, n.s > 0.05).
Interpretation of results
Spontaneous contractions were significantly (p < 0.05) and rapidly reduced within 10 minutes by G2 and E2, supporting a hormonal, non-genomic effect on smooth muscle tone. The percentage relaxation induced by G1 and E2 was non-significantly different, indicating activation of GPER induces smooth muscle relaxation.
Overall these data show that promotion of non-genomic estrogen action is a potential mechanism for therapeutic targeting of the dynamic component of BPH.
Concluding message
In this study, we investigated the effects of estrogens on smooth muscle contractility of the human prostate. We describe a rapid, non-genomic effect on prostate contractility that we show is mediated by the G-Protein Estrogen Receptor (GPER). As contractility is significantly upregulated in men with Benign Prostatic Hyperplasia (BPH), we propose pharmacological targeting of the GPER may be clinically beneficial.
Disclosures
Funding Funding was provided by the Deutsche Forschungsgemeinschaft (GRK 1871) and Monash University, Australia, to the International Research Training Group (IRTG) between Justus-Liebig University Giessen and Monash University. S. Lee was supported by the Australian Government Research Training Program Scholarship. G. Risbridger was supported by an Australian NH&MRC SPRF (ID# 1102752). Clinical Trial No Subjects Human Ethics Committee Human prostatic tissue was collected with informed written consent from patients and approval from the Cabrini Human Research Ethics Committee (13-14-04-08), Epworth HealthCare Human Ethics Committee (53611) and Monash University Human Research Ethics Committee (2004/145). Helsinki Yes Informed Consent Yes
03/02/2023 05:02:08