Abstract
Purpose: Diabetes is associated with increased lower urinary tract symptom (LUTS) severity. An underlying cause of LUTS is increased prostate smooth muscle tone. A critical regulator of prostate innervation and tone is nitric oxide (NO), produced by nitric oxide synthase (NOS). Since NO regulates proliferation and relaxation, and NOS signaling is altered in patients with LUTS, we propose that decreased NO in diabetic patients leads to increased LUTS. We examined this hypothesis by quantifying changes in NOS signaling in the BB/WOR diabetic rat prostate. Materials and Methods:Protein and RNA abundance and localization of NOS I, -II and -III were examined in control and diabetic BB rat prostate by Real time RT-PCR, Western, immunohistochemical analysis and in situ.Morphological changes were examined by electron microscopy (EM), and TUNEL. Results:NosIII is the most abundant isoform in ventral and dorsal prostate. NOS I, -II and -III protein and RNA localize to ductal epithelium. NOS III protein and RNA were significantly decreased in diabetic prostate. Apoptosis was increased in diabetic dorsal prostate. EM of the diabetic dorsal prostate showed abundant protein filled vacuoles and abnormal cytoplasmic morphology indicative of apoptosis. Conclusions:Since NOS III is the most abundant form of NOS in the prostate diabetes may contribute to LUTS severity by down regulating NO, which may lead to increased proliferation in ductal epithelium
Highlights
Male lower urinary tract symptoms (LUTS) encompass a variety of urologic symptoms including increased obstructive and storage symptoms
Since nitric oxide synthase (NOS) III is the most abundant form of NOS in the prostate diabetes may contribute to LUTS severity by down regulating nitric oxide (NO), which may lead to increased proliferation in ductal epithelium
If NOS abundance is decreased in diabetic prostate, as was shown in other genitourinary organs such as the penis [12], this reduction in associated smooth muscle tone may manifest as obstructive and/or irritative voiding and present a putative mechanism of how LUTS severity is increased in diabetic patients
Summary
Male lower urinary tract symptoms (LUTS) encompass a variety of urologic symptoms including increased obstructive and storage symptoms. Previous studies have focused on age and androgen fluctuation as potential risk factors, there is increasing evidence that a diverse group of comorbidities including diabetes mellitus (DM), obesity and components of the metabolic syndrome, contribute to LUTS severity [4,5]. If NOS abundance is decreased in diabetic prostate, as was shown in other genitourinary organs such as the penis [12], this reduction in associated smooth muscle tone may manifest as obstructive and/or irritative voiding and present a putative mechanism of how LUTS severity is increased in diabetic patients. We hypothesize that decreased NOS signaling in diabetic rats will cause morphological changes in the prostate that may contribute to increased symptom severity of LUTS in diabetic men
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