Project Abstract
Benign prostatic hyperplasia (BPH) is a disease impacting much of the aging male population, affecting 50% of
men 50 and older, and increasing to 90% of men 80 and older. The etiology of BPH is complex and multifactorial,
though proliferation, smooth muscle dysfunction and fibrosis within the prostate are often considered the largest
contributing factors, in addition to age. Estrogen signaling via receptors (ERs) within the prostate have been
shown to play conflicting roles, with ERa associated with increased proliferation while ERß with apoptotic
processes. Current BPH therapeutic strategies target androgen biosynthesis without considering that androgens
are regularly converted to estrogenic ligands in the steroid hormone signaling pathway. I hypothesize that
estrogen signaling within the prostate, specifically ERa activity, induces prostatic fibrosis and thus
contributes to the development of lower urinary tract dysfunction (LUTD) and BPH. I aim to evaluate this
hypothesis through the use of mass spectrometry (MS)-based proteomics analyses. With the development of
high resolution and accurate mass instrumentation, MS has become the preferred technique for deep, targeted
and global proteomic profiling investigations. In addition, the development of mass spectrometry imaging (MSI)
allows for high throughput analysis of protein and peptide species in a biological tissue with no prior knowledge,
thus obtaining critical spatial information of hundreds of analytes in a single imaging run. I plan to utilize the high
sensitivity and selectivity of both MSI and traditional chromatography-based LC-MS/MS experiments to reach
the following goals: 1) to determine if ERa agonism in mice promotes prostatic fibrosis and LUTD and 2) to
uncover if loss of ERa function decreases prostatic fibrosis in vivo. Collectively, these aims will both facilitate the
use of MS-based strategies in urologic research and yield novel insights into the complex roles that estrogen
receptor alpha plays within the prostate.
