PUTATIVE MELATONIN RECEPTORS IN BENIGN HUMAN PROSTATE TISSUE

Melatonin, secreted by the pineal gland at night, inhibits pubertal de velopment of rats and presumably men. In addition, it may directly sup press prostate growth in the adult rat. To investigate the possibility for a causal relationship between the age-related decline in melatoni n production and increase in prevalence of benign prostate hypertrophy (BPH) in man, the presence of melatonin binding sites in human BPH ti ssue was examined. In vitro autoradiography indicated specific I-125-l abeled melatonin (I-125-melatonin) binding in the prostate, localized to the glandular epithelium. Separation and subcellular fractionation indicated that these sites were associated with the microsomal fractio n of the epithelial cells. Kinetic and equilibrium I-125-melatonin bin ding experiments revealed that the binding was time dependent and reve rsible, with an apparent half saturation at 140 pmol/L. Competition ex periments indicated high and low affinity melatonin binding sites; bin ding was inhibited by melatonin (IC50 1 nmol/L and 1 mu mol/L, respect ively) and partially by the putative melatonin antagonist, N-(2,4 dini trophenyl)-5-methoxytryptamine (ML-23; IC50 0.1 nmol/L). Serotonin and 6-hydroxymelatonin were less potent, whereas up to 0.1 mmol/Lol/L of B-methoxytryptamine, 6-methoxymelatonin, and tryptamine caused only a partial reduction in specific binding. The guanine nucleotide analogs, guanosine 5'-O-[3-thiotriphosphate] and guanosine 5'-O-[2-thio-diphos phate], inhibited specific I-125-melatonin binding, whereas B'-guanyly l imidodiphosphate was less potent. The results indicate putative mela tonin receptors in the human prostate epithelium.