FUNCTIONAL MELATONIN RECEPTORS IN HUMAN PROSTATE EPITHELIAL-CELLS

Melatonin, secreted nocturnally by the pineal gland, affects gonadal g rowth and pubertal development in rodents and, presumably, in humans. Recently, we have found, using I-125-labeled melatonin as a probe, spe cific melatonin binding sites in the human benign prostate tissue; the se sites were primarily associated with the microsomal fraction of the epithelial cells. In the present study, we have explored I-125-melato nin binding sites in human benign prostate epithelial cells in culture and investigated the effects of melatonin on growth and viability of these cells. I-125-melatonin bound to the prostate cells with high (K- d = 68 pM) affinity. Competition experiments revealed that specific bi nding was inhibited by subnanomolar concentrations of melatonin and 2- iodomelatonin, whereas serotonin and 5-methoxytryptamine reduced the b inding only partially. Melatonin (10 pM-10 nM) inhibited the incorpora tion of H-3-thymidine and H-3-uridine into the prostate epithelial cel ls in a dose-dependent manner. Inhibition was transient, and the incor poration recovered to control levels within less than 24 h. Protein sy nthesis as measured by the incorporation of S-35-methionine into cell proteins decayed to minimal levels about 2 h after addition of melaton in, and its recovery was slower compared with that of H-3-thymidine or H-3-uridine incorporation. Melatonin treatment (1 nM) for 2-7 days in hibited cell growth and markedly increased the percentage of nonviable cells in culture, measured by the trypan blue exclusion assay. The re sults demonstrate high affinity melatonin receptors in the human benig n prostate epithelial cells, which may affect cell growth and viabilit y.