Effect of increasing ratio of estrogen: Androgen on proliferation of normal human prostate stromal and epithelial cells, and the malignant cell line LNCaP

Abstract

BACKGROUND Changes in steroid ratios seen in the aging male are thought to promote prostate disease. The aims of this study were to compare the effects of varied ratios of steroids on growth of normal stromal and epithelial cell isolates, and the prostate cancer cell line, LNCaP. METHODS The effect of altered steroid ratios on cell proliferation of normal stromal (PrSC) and epithelial (PrEC) prostate cells, and the malignant cell line, LNCaP, were assessed. RESULTS Increasing the ratios of both estrogen:dihydrotestosterone (DHT) and DHT:estrogen, stimulated PrSC proliferation, with increasing estrogen:DHT having the greatest effect. LNCaP proliferation was increased significantly by both steroids, but altered ratios had no additional effect. PrEC proliferation was unaffected when cells were grown alone, despite presence of androgen receptors (AR) and estrogen receptors (ER). When grown in co-culture PrEC cell proliferation was significantly increased by treatments. CONCLUSIONS PrSC proliferation is stimulated by an increasing ratio of estrogen:androgen. Proliferation of normal epithelial cells is stimulated as a result of an indirect action of steroids mediated by stromal cells. Malignant prostate cancer cells have an altered response in comparison.