Altered prostate epithelial development in mice lacking the androgen receptor in stromal fibroblasts

Shengqiang Yu, Chiuan Ren Yeh, Yuanjie Niu, Hong Chiang Chang, Yu Chieh Tsai, Harold L. Moses, Chih Rong Shyr, Chawnshang Chang*, Shuyuan Yeh

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

62 Scopus citations


BACKGROUND Androgens and the androgen receptor (AR) play important roles in the development of male urogenital organs. We previously found that mice with total AR knockout (ARKO) and epithelial ARKO failed to develop normal prostate with loss of differentiation. We have recently knocked out AR gene in smooth muscle cells and found the reduced luminal infolding and IGF-1 production in the mouse prostate. However, AR roles of stromal fibroblasts in prostate development remain unclear. METHODS To further probe the stromal fibroblast AR roles in prostate development, we generated tissue-selective knockout mice with the AR gene deleted in stromal fibroblasts (FSP-ARKO). We also used primary culture stromal cells to confirm the in vivo data and investigate mechanisms related to prostate development. RESULTS The results showed cellular alterations in the FSP-ARKO mouse prostate with decreased epithelial proliferation, increased apoptosis, and decreased collagen composition. Further mechanistic studies demonstrated that FSP-ARKO mice have defects in the expression of prostate stromal growth factors. To further confirm these in vivo findings, we prepared primary cultured mouse prostate stromal cells and found knocking down the stromal AR could result in growth retardation of prostate stromal cells and co-cultured prostate epithelial cells, as well as decrease of some stromal growth factors. CONCLUSIONS Our FSP-ARKO mice not only provide the first in vivo evidence in Cre-loxP knockout system for the requirement of stromal fibroblast AR to maintain the normal development of the prostate, but may also suggest the selective knockdown of stromal AR might become a potential therapeutic approach to battle prostate hyperplasia and cancer.

Original languageEnglish
Pages (from-to)437-449
Number of pages13
Issue number4
StatePublished - 03 2012
Externally publishedYes


  • Cre-loxP
  • androgen receptor
  • epithelium
  • fibroblast specific protein
  • prostate


Dive into the research topics of 'Altered prostate epithelial development in mice lacking the androgen receptor in stromal fibroblasts'. Together they form a unique fingerprint.

Cite this