# Estrogens stimulate prostatic collagen synthesis to drive fibrosis and LUTD

> **NIH NIH U54** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $174,941

## Abstract

PROJECT SUMMARY
Healthcare costs for lower urinary tract symptoms (LUTS) ascribed to benign prostatic hyperplasia (BPH) are in
the billions of dollars annually. Therapies for BPH/LUTS target smooth muscle contractility with α-blockers or
hyperplasia with 5α-reductase inhibitors. Although these therapies can be medicinal, they are not
effective/durable for all; this leaves millions of men in the US needing more effective therapies. The standard of
medical care for BPH/LUTS currently over-treats this patient population, in part due to a poor understanding of
etiology and progression. There is an apparent need to define what BPH represents in patient populations as
well as to identify the true anatomic, cellular, and molecular causes of the disease. This may elucidate the true
causes in development and progression of the disease as well as institute effective therapies. The overarching
goal of the O’Brien Center for Benign Urology Research is to identify the mechanisms that result in lower urinary
tract dysfunction and prostate-related LUTS. Previous studies have demonstrated prostatic collagen deposition
coincident with prostate stiffness, LUTS, and failed medical treatment supporting the concept that BPH/LUTS is,
in part, a fibrotic disease. However, this brings up a translational challenge because treatment of prostatic fibrosis
cannot occur until cellular and molecular pathways have been identified. As such, the goal is to identify the
anatomical, cellular, and molecular origins of prostate fibrosis in men with BPH/LUTS. Recently, estrogens,
specifically signaling through estrogen receptor (ER)α, was discovered to be necessary for the development of
prostatic fibrosis and LUTD in mice. Although, multiple stromal and epithelial cells express ERα, a subpopulation
of ERα positive prostatic fibroblasts and/or smooth muscle cells could be responsible for increased collagen
deposition. These cells are sensitive to estrogens and produce large amounts of collagen in vitro and in vivo.
Aim 1 will address the ER molecular mechanism of action in the transcription of Col1a1 by determining if classical
or non-classical ER signaling is necessary. Next, collagen accumulation has been linked with BPH/LUTS, but it
is uncertain if collagen/fibrosis acts independently or in collaboration with prostate hyperplasia; Aim 2 will test
the hypothesis that gain of collagen function promotes LUTD independent of prostate hyperplasia. Clinical
translation of our findings is a goal of the center; Aim 3 will test the hypothesis that clinically relevant antifibrotics
are effective in the treatment of prostatic fibrosis. Lastly, stratification of men with fibrotic prostates is imperative
to increase treatment efficacy. To address this challenge, advanced and novel collagen MR imaging techniques
will be used to assess whether prostatic fibrosis can be identified in preclinical models. By establishing cellular
and molecular mechanistic connections between fibrosis and BPH/LUTS as...

## Key facts

- **NIH application ID:** 10022317
- **Project number:** 5U54DK104310-07
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** WILLIAM A RICKE
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $174,941
- **Award type:** 5
- **Project period:** 2014-09-24 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10022317

## Citation

> US National Institutes of Health, RePORTER application 10022317, Estrogens stimulate prostatic collagen synthesis to drive fibrosis and LUTD (5U54DK104310-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10022317. Licensed CC0.

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