TY - JOUR
T1 - The Effects of Age on Prostatic Responses to Oxytocin and the Effects of Antagonists
AU - Badshah, Masroor
AU - Ibrahim, Jibriil
AU - Su, Nguok
AU - Whiley, Penny
AU - Whittaker, Michael
AU - Exintaris, Betty
N1 - Funding Information:
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. M. Badshah was supported by the Monash Graduate and Monash Departmental Scholarships.
Funding Information:
I would like to acknowledge the Monash Hudson Histology Platform, especially Camilla Cohen and Angela Vais, for providing professional histology services such as paraffin embedding, staining, and imaging tissue sections at their platform. I would also like to acknowledge Jaya Jayaseelan and Monash Animal Research Platform Clayton for providing the young and aged rats. Furthermore, I would acknowledge Julie Stafford for the proof reading and editing. Project administration, Hudson Institute of Medical Research; funding acquisition, Deutsche Forschungsgemeinschaft (GRK 1871) and Monash University, Australia, to the International Research Training Group (IRTG) between Justus-Liebig University Giessen and Monash University; M.B. was supported by Monash Graduate Scholarship.
Publisher Copyright:
© 2023 by the authors.
PY - 2023/11
Y1 - 2023/11
N2 - Benign prostatic hyperplasia (BPH) is an age-related enlargement of the prostate with urethral obstruction that predominantly affects the middle-aged and older male population, resulting in disruptive lower urinary tract symptoms (LUTS), thus creating a profound impact on an individual’s quality of life. The development of LUTS may be linked to overexpression of oxytocin receptors (OXTR), resulting in increased baseline myogenic tone within the prostate. Thus, it is hypothesised that targeting OXTR using oxytocin receptor antagonists (atosiban, cligosiban, and β-Mercapto-β,β-cyclopentamethylenepropionyl1, O-Me-Tyr2, Orn8]-Oxytocin (ßMßßC)), may attenuate myogenic tone within the prostate. Organ bath and immunohistochemistry techniques were conducted on prostate tissue from young and older rats. Our contractility studies demonstrated that atosiban significantly decreased the frequency of spontaneous contractions within the prostate of young rats (**** p < 0.0001), and cligosiban (* p < 0.05), and ßMßßC (**** p < 0.0001) in older rats. Additionally, immunohistochemistry findings revealed that nuclear-specific OXTR was predominantly expressed within the epithelium of the prostate of both young (*** p < 0.001) and older rats (**** p < 0.0001). In conclusion, our findings indicate that oxytocin is a key modulator of prostate contractility, and targeting OXTR is a promising avenue in the development of novel BPH drugs.
AB - Benign prostatic hyperplasia (BPH) is an age-related enlargement of the prostate with urethral obstruction that predominantly affects the middle-aged and older male population, resulting in disruptive lower urinary tract symptoms (LUTS), thus creating a profound impact on an individual’s quality of life. The development of LUTS may be linked to overexpression of oxytocin receptors (OXTR), resulting in increased baseline myogenic tone within the prostate. Thus, it is hypothesised that targeting OXTR using oxytocin receptor antagonists (atosiban, cligosiban, and β-Mercapto-β,β-cyclopentamethylenepropionyl1, O-Me-Tyr2, Orn8]-Oxytocin (ßMßßC)), may attenuate myogenic tone within the prostate. Organ bath and immunohistochemistry techniques were conducted on prostate tissue from young and older rats. Our contractility studies demonstrated that atosiban significantly decreased the frequency of spontaneous contractions within the prostate of young rats (**** p < 0.0001), and cligosiban (* p < 0.05), and ßMßßC (**** p < 0.0001) in older rats. Additionally, immunohistochemistry findings revealed that nuclear-specific OXTR was predominantly expressed within the epithelium of the prostate of both young (*** p < 0.001) and older rats (**** p < 0.0001). In conclusion, our findings indicate that oxytocin is a key modulator of prostate contractility, and targeting OXTR is a promising avenue in the development of novel BPH drugs.
KW - BPH
KW - LUTS
KW - oxytocin
KW - oxytocin receptor antagonists
UR - https://www.scopus.com/pages/publications/85178377902
U2 - 10.3390/biomedicines11112956
DO - 10.3390/biomedicines11112956
M3 - Article
C2 - 38001957
AN - SCOPUS:85178377902
SN - 2227-9059
VL - 11
JO - Biomedicines
JF - Biomedicines
IS - 11
M1 - 2956
ER -