Stromal growth and epithelial cell proliferation in ventral prostates of liver X receptor knockout mice

With specific liver X receptor alpha and beta (LXR alpha and LXR beta) antibodies, we found that LXR alpha is strongly expressed in the luminal and basal cells of prostatic epithelium. The ventral prostates (VP) of LXR alpha(-/-) mice are characterized by the presence of smooth-muscle actin-positive stromal overgrowth around the prostatic ducts and by numerous fibrous nodules pushing into the ducts and causing obstruction, so that most of the ducts were extremely dilated. BrdU labeling and Ki67 staining revealed epithelial and stromal proliferation in the fibrous nodules. However, the dense stroma surrounding the ducts was not positive for proliferation markers. There was no detectable difference between WT and LXR alpha(-/-) mice VP in the expression of the androgen receptor, but there was an increase in nuclear expression of Snail and Smad 2/3, indicating enhanced TGF-beta signaling. Upon treatment of WT mice for 3 months with the LXR agonist T2320 or for 3 weeks with beta-sitosterol, LXR alpha was downregulated, and a VP phenotype similar to that of LXR alpha(-/-) mice resulted. Weconclude that in rodents, LXR alpha seems to control VP stromal growth and that LXR alpha(-/-) mice may be a useful model to study prostatic stromal hyperplasia. Because LXR alpha is expressed in the epithelium, the excessive stromal growth in LXR alpha(-/-) mice indicates that LXR alpha is essential for epithelial stromal communication.