Melatonin receptors in human prostate epithelial cells

Melatonin plays a major role in the control of reproductive physiology (1): in seasonal breeders it mediates the effects of short photoperiod on gonadal physiology, and in the rat it delays the development of the accessory sex organs and the onset of puberty. In humans, reports on coincidence of pineal tumors and low plasma melatonin with precocious puberty and on melatonin-related hypogonadotrophic hypogonadism (2,3) support a role for the pineal hormone in sexual maturation and the development of accessory sex organs. Nocturnal melatonin levels decrease concurrently with human pubertal development and a further decline is seen in old age (4). The role of melatonin in human physiology to date has been focused primarily on the pituitary-gonadal axis but recent studies suggest direct effects of melatonin on peripheral organs. Benign prostatic hyperplasia (BPH) is a disease of men characterized histologically by the formation of non-malignant prostatic nodules and clinically by symptoms of urinary obstruction caused by abnormal prostatic growth narrowing the urethral lumen. The occurrence of BPH increases sharply in men over 50 years of age. Histological evidence of BPH is seen in almost all men by the age of 80 (5). Suppressive effects of melatonin on prostate growth in humans has not been demonstrated yet. In addition, neither chronic or acute milligram doses of melatonin were effective in influencing testosterone in the adult man suggesting that the output of luteinizing hormone (LH) from the pituitary may not be affected (6). Melatonin has been shown to stimulate 3 alpha/beta reductase activity with no effect on 5 alpha reductase activity in BPH tissue samples (7). Hence, melatonin may have a direct suppressive influence on the prostate or on autocrine mechanisms regulating its physiology. To examine the possibility that melatonin plays a role in prostate growth in aging men we have recently explored human BPH tissue for the presence of melatonin binding sites and responses. The present review summarizes the results of published and new studies demonstrating functional melatonin receptors in the human benign prostate.