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

J Proteome Res. 2020 Apr 3;19(4):1375-1382. doi: 10.1021/acs.jproteome.9b00451. Epub 2020 Mar 16.


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.

Keywords: endocrine disruption; lower urinary tract symptoms; prostate; proteomics; spatiotemporal; urine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Hormones
  • Humans
  • Hydrogen Peroxide
  • Male
  • Mice
  • Proteomics*
  • Urinary Bladder Neck Obstruction*
  • X-Ray Microtomography


  • Hormones
  • Hydrogen Peroxide