Identification of an activin-follistatin growth modulatory system in the human prostate: Secretion and biological activity in primary cultures of prostatic epithelial cells

Purpose: To determine if the activin/follistatin system is present in human prostate tissue and primary cultures of prostatic epithelium and if these growth factors play a role in the control of epithelial cell growth, Materials and Methods: Cells derived directly from human prostates were stu died to determine: a) if they secrete activin and follistatin, and b) if th ey are growth inhibited by activin. Primary cell cultures were established from tissues removed from 13 unselected prostate carcinoma patients in orde r to examine the secretion of activin and follistatin and test the effects of these proteins on cell proliferation. Results: Both primary explant cells and epithelial cells isolated and sub-c ultured from explant cultures secreted activin A and follistatin. Treatment of cultured cells with recombinant human activin A resulted in a dose-depe ndent inhibition of thymidine incorporation, with an IC50 of 0.22 nM, Recom binant follistatin neutralized the inhibitory effects of activin A on cell proliferation whilst adding follistatin alone enhanced thymidine incorporat ion, suggesting a similar neutralizing effect on the endogenous activin pro duced by these cells. Conclusion: These results demonstrate that cells derived from human prostat e tissue secrete activin and follistatin and, as observed in human prostate cancer cell lines, activin inhibited the growth of prostatic epithelial ce lls. Also consistent with our earlier studies of prostate cancer cell lines , the biological activity of activin was neutralized by follistatin. These observations support the hypothesis that the activin/follistatin system pla ys an important role in the local regulation of human prostate cell growth.