Distinct Function of Estrogen Receptor α in Smooth Muscle and Fibroblast Cells in Prostate Development

Estrogen signaling, through estrogen receptor (ER)alpha, has been shown to cause hypertrophy in the prostate. Our recent report has shown that epithelial ER alpha knockout (KO) will not affect the normal prostate development or homeostasis. However, it remains unclear whether ER alpha in different types of stromal cells has distinct roles in prostate development. This study proposed to elucidate how KO of ER alpha in the stromal smooth muscle or fibroblast cells may interrupt cross talk between prostate stromal and epithelial cells. Smooth muscle ER alpha KO (smER alpha KO) mice showed decreased glandular infolding with the proximal area exhibiting a significant decrease. Fibroblast ER alpha KO mouse prostates did not exhibit this phenotype but showed a decrease in the number of ductal tips. Additionally, the amount of collagen observed in the basement membrane was reduced in smER alpha KO prostates. Interestingly, these phenotypes were found to be mutually exclusive among smER alpha KO or fibroblast ER alpha KO mice. Compound KO of ER alpha in both fibroblast and smooth muscle showed combined phenotypes from each of the single KO. Further mechanistic studies showed that IGF-I and epidermal growth factor were down-regulated in prostate smooth muscle PS-1 cells lacking ER alpha. Together, our results indicate the distinct functions of fibroblast vs. smER alpha in prostate development. (Molecular Endocrinology 27: 38-49, 2013)