Spatiotemporal Proteomics Reveals the Molecular Consequences of Hormone Treatment in a Mouse Model of Lower Urinary Tract Dysfunction

Benign prostatic
hyperplasia and related lower urinary tract symptoms
remain common, costly, and impactful issues for aging males. The etiology
and pathogenesis are multifactorial and include steroid hormone changes
and inflammation. Noninvasive markers could one day inform personalized
medicine, but interindividual variation and lack of healthy age-matched
controls hamper research. Experimental models are appealing for insight
into disease mechanisms. Here, we present a spatiotemporal proteomics
study in a mouse model of hormone-induced urinary dysfunction. Urine
samples were collected noninvasively across time: before, during,
and after disease onset. A microcomputed tomography analysis implicated
the prostate as a spatially relevant contributor to bladder outlet
obstruction. Prostates were collected after disease onset and compared
with control mice. Notable changes in urine include proteins representing
oxidative stress defense and acute phase inflammatory response processes.
In the prostate, hormone treatment led to perturbations related to
an oxidative stress response and H2O2 metabolism.
Several protein changes coincided in both urine and the prostate tissue,
including glutathione peroxidase 3, glutathione hydrolase 1 proenzyme,
and vitamin D-binding protein. This study supports the concept of
noninvasive urinary biomarkers for prostate disease diagnostics. Oxidative
stress and acute phase inflammatory processes were identified as key
consequences of hormone-induced bladder outlet obstruction. Future
research into antioxidants and anti-inflammatories in prostate diseases
appears promising.