Renaissance of an animal model for human benign prostatic hyperplasia using mice subject to long-term treatment with estrogen

In previous light and electron-microscopic analyses, human benign prostatic hyperplasia was shown to be predominantly a stromal disease. Smooth muscle cell activation and stromal overgrowth was achieved in beagle dogs following estrogen administration; this experiment indicates that estrogens play a role in the induction of stromal growth in the prostate. In the present investigation, histological and electron-microscopic studies on the estrogen-induced enlargement of the prostate in a/J mice were performed. After treatment with estrogens (0.1 mg estradiol valerianate per week for 12 weeks) two types of stromal reaction patterns were observed: 1. tightly packed smooth muscle cells with formation of whorl-like nodules, 2. loose interstitial tissue surrounding the stromal and glandular cells. Electron microscopy of the stromal tissue reveals fibrocytes, smooth muscle cells and bundles of collagen fibres in between. The tightly packed smooth muscle cells are highly activated (increased amount of cytoplasmic organelles). Similar to the stromal tissue, the glandular cells do not show a homogeneous reaction to estrogen stimulation. If the glandular cells were surrounded by loose interstitial tissue, only mild metaplastic changes were observed; however, inside the whorl-like nodules of the smooth muscle cells, severe metaplastic changes were observed.