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Updated: May 31, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Smooth muscle cell-specific knockout of androgen receptor: a new model for prostatic disease
Michelle Welsh1, Lindsey Moffat, Alan McNeilly
1Medical Research Council Centre for Reproductive Health, The Queen's Medical Research Institute, Edinburgh, EH16 4TJ, Scotland, United Kingdom. m.welsh@beatson.gla.ac.uk
Abstract:
Androgen-driven stromal-epithelial interactions play a key role in normal prostate development and function as well as in the progression of common prostatic diseases such as benign prostatic hyperplasia and prostate cancer. However, exactly how, and via which cell type, androgens mediate their effects in the adult prostate remains unclear. This study investigated the role for smooth muscle (SM) androgen signaling in normal adult prostate homeostasis and function using mice in which androgen receptor was selectively ablated from prostatic SM cells. In adulthood the knockout (KO) mice displayed a 44% reduction in prostate weight and exhibited histological abnormalities such as hyperplasia, inflammation, fibrosis, and reduced expression of epithelial, SM, and stem cell identify markers (e.g. p63 reduced by 27% and Pten by 31%). These changes emerged beyond puberty and were not explained by changes in serum hormones. Furthermore, in response to exogenous estradiol, adult KO mice displayed an 8.5-fold greater increase in prostate weight than controls and developed urinary retention. KO mice also demonstrated a reduced response to castration compared with controls. Together these results demonstrate that prostate SM cells are vital in mediating androgen-driven stromal-epithelial interactions in adult mouse prostates, determining cell identity and function and limiting hormone-dependent epithelial cell proliferation. This novel mouse model provides new insight into the possible role for SM androgen action in prostate disease.
Insights
Prostate smooth muscle cells mediate androgen effects, regulating prostate size and function. Ablating androgen receptors in these cells causes prostate abnormalities and disease-like changes.
Area of Science:
- Urology
- Endocrinology
- Cell Biology
Background:
- Androgen signaling is crucial for prostate development and disease.
- The specific cell types mediating androgen effects in the adult prostate are not fully understood.
Purpose of the Study:
- To investigate the role of androgen signaling in prostatic smooth muscle (SM) cells in adult mouse prostate homeostasis and function.
Main Methods:
- Selective ablation of androgen receptor in prostatic SM cells of mice (knockout model).
- Analysis of prostate weight, histology, cell marker expression, serum hormone levels, and response to hormonal stimuli (estradiol, castration).
Main Results:
- Knockout mice showed reduced prostate weight (44%), hyperplasia, inflammation, fibrosis, and decreased expression of key cell markers.
- Changes occurred post-puberty and were independent of serum hormone levels.
- Knockout mice exhibited exaggerated prostate growth with estradiol and impaired response to castration.
Conclusions:
- Prostatic SM cells are essential mediators of androgen-driven stromal-epithelial interactions in adult mice.
- SM androgen signaling is vital for maintaining prostate cell identity, function, and limiting epithelial proliferation.
- This study provides a novel model for understanding the role of SM androgen action in prostate disease.
