Imbalances in the epithelial-stromal interactions are important in the pathogenesis of prostate cancer. However, we know little about androgenic regulation in the stroma of prostate cancer. We examined the cancer-stromal interaction paying attention to androgen responsiveness of stromal side. In co-culture, PC3 and LNCaP cells did not affect dihydrotestosterone (DHT)-dependent growth of prostate stromal cells (PrSCs), but DU 145 cells significantly reduced it. Conditioned medium from DU 145 cells (DU145-CM) also inhibited DHT-dependent PrSCs growth, androgen receptor (AR) expression, and prostate specific antigen transcription. Although the inhibitory effect of DU145-CM was not affected by neutralizing antibody against EGF, FGF-2, or TNF-alpha, pretreatment with testosterone-Sepharose partially reduced the inhibitory ability of DU145-CM. These results suggest that DU145 cells produce inhibitory factors for androgen responsiveness, including steroid-binding protein(s), and these may participate in crosstalk between DU145 cells and PrSCs as modulators of androgen. (C) 2003 Elsevier Science (USA). All rights reserved.