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Updated: May 31, 2026
Murine Prostate Micro-dissection and Surgical Castration
Published on: May 11, 2016
Increased CK5/CK8-positive intermediate cells with stromal smooth muscle cell atrophy in the mice lacking prostate
Yuanjie Niu1, Juan Wang, Zhiqun Shang
1Chawnshang Chang Sex Hormone Research Center, Tianjin Institute of Urology, Tianjin Medical University, Tianjin, China. niuyuanjie@gmail.com
Abstract:
Results from tissue recombination experiments documented well that stromal androgen receptor (AR) plays essential roles in prostate development, but epithelial AR has little roles in prostate development. Using cell specific knockout AR strategy, we generated pes-ARKO mouse with knock out of AR only in the prostate epithelial cells and demonstrated that epithelial AR might also play important roles in the development of prostate gland. We found mice lacking the prostate epithelial AR have increased apoptosis in epithelial CK8-positive luminal cells and increased proliferation in epithelial CK5-positive basal cells. The consequences of these two contrasting results could then lead to the expansion of CK5/CK8-positive intermediate cells, accompanied by stromal atrophy and impaired ductal morphogenesis. Molecular mechanism dissection found AR target gene, TGF-β(1), might play important roles in this epithelial AR-to-stromal morphogenesis modulation. Collectively, these results provided novel information relevant to epithelial AR functions in epithelial-stromal interactions during the development of normal prostate, and suggested AR could also function as suppressor in selective cells within prostate.
Insights
Prostate epithelial androgen receptor (AR) is crucial for gland development, contrary to previous beliefs. Removing epithelial AR disrupts cell balance, impacting prostate morphogenesis and stromal interactions.
Area of Science:
- Reproductive biology
- Developmental biology
- Molecular endocrinology
Background:
- Stromal androgen receptor (AR) is known to be essential for prostate development.
- Epithelial AR's role in prostate development has been considered minimal based on prior studies.
Purpose of the Study:
- To investigate the role of epithelial AR in prostate gland development using a cell-specific knockout mouse model.
- To elucidate the molecular mechanisms underlying epithelial AR function in prostate development and epithelial-stromal interactions.
Main Methods:
- Generation of prostate epithelial-specific AR knockout (pes-ARKO) mice.
- Analysis of prostate tissue morphology, cell proliferation (CK5, CK8 markers), and apoptosis.
- Investigation of AR target genes, including TGF-β(1), to understand molecular pathways.
Main Results:
- Mice lacking epithelial AR exhibited increased apoptosis in CK8-positive luminal cells and enhanced proliferation in CK5-positive basal cells.
- These cellular changes led to the expansion of CK5/CK8-positive intermediate cells, stromal atrophy, and impaired ductal morphogenesis.
- The AR target gene TGF-β(1) was implicated in mediating epithelial AR's influence on stromal morphogenesis.
Conclusions:
- Epithelial AR plays a significant role in prostate development, challenging previous assumptions.
- Epithelial AR regulates epithelial-stromal interactions crucial for normal prostate morphogenesis.
- AR can function as a suppressor in specific prostate epithelial cell populations, influencing gland development.
