Cross talk between melatonin and TGF beta I in human benign prostate epithelial cells

BACKGROUND. Epithelial cells from the human benign prostate express melaton in receptors which effect transient suppression of DNA synthesis and sustai ned attenuation of growth. The role of transforming growth factor-beta 1 (T GF beta 1), which is produced in prostate epithelial cells and inhibits the ir growth, was examined in the action of melatonin. METHODS. The effects of melatonin and TGF beta 1 and their combination on H -3-thymidine incorporation were assessed. The possibility that melatonin ef fected TGF beta 1 release from cells was studied. RESULTS. Incubation of the cells with TGF beta 1 resulted in a time- and do se-dependent inhibition of H-3-thymidine incorporation into cells. Melatoni n (10-500 pM) inhibited H-3-thymidine incorporation, and its effects were a ttenuated at higher (1-10 nM) concentrations. In the presence of submaximal doses of TGF beta 1,the inhibitory effect of melatonin was maintained over the entire concentration range tested (10 pM-10 nM). The inhibition of H-3 -thymidine incorporation by TGF beta 1 was more pronounced in the absence o f dihydrotestosterone (DHT) than in its presence, and melatonin had no furt her effect. Melatonin enhanced the release of proteins from cells, among th em proteins recognized by specific TGF beta 1 antisera. The TGF beta 1-neut ralizing antisera prevented the inhibitory action of melatonin on H-3-thymi dine incorporation into cells. CONCLUSIONS. These data indicate a role for TGF beta 1 in the melatonin-med iated attenuation of benign prostate epithelial cell growth. (C) 1999 Wiley -Liss, Inc.