Relevance of STIM/Orai Calcium Entry System Hyperactivation in Human Prostate Contractility in Benign Prostate...

Area of Science:

• Urology
• Cell Biology
• Pharmacology

Background:

• Benign prostate hyperplasia (BPH) causes prostate enlargement and lower urinary tract symptoms (LUTS).
• Prostate hypercontractility is a potential contributor to BPH-related LUTS.
• The stromal interaction molecule (STIM)/Orai calcium entry system's role in BPH-related contractions is not fully understood.

Purpose of the Study:

• To investigate the impact of inhibiting the STIM/Orai system on prostate and bladder neck contractions in BPH patients.
• To compare these effects with tissues from organ donors without BPH.
• To assess STIM-1, Orai1, and Orai3 protein expression in BPH prostate tissues.

Main Methods:

• Isometric tension recording of human prostate (HP) and bladder neck (HB) strips from BPH patients and organ donors (ODs).
• Application of YM-58483 (20 µM) to inhibit the STIM/Orai system.
• Western blotting and immunofluorescence to determine STIM-1, Orai1, and Orai3 protein expression and localization.

Main Results:

• STIM/Orai inhibition significantly reduced norepinephrine-induced and neurogenic contractions in HP from BPH patients.
• These inhibitory effects were not observed in HP from ODs or in HB from BPH patients.
• STIM-1 protein expression was significantly elevated in HP from BPH patients compared to controls.

Conclusions:

• The STIM/Orai system plays a significant functional role in prostate contractile tone in the presence of BPH, likely due to increased STIM-1 expression.
• Inhibiting the STIM/Orai system may offer a therapeutic strategy for managing BPH by reducing prostatic hypercontraction.
• Targeting the STIM/Orai pathway presents a potential avenue for alleviating LUTS in BPH patients.