Direct Effects of Melatonin and Serotonin on the Biosynthesis of Testosterone in Rat Leydig Cells

Abstract

Previous studies indicate that melatonin (MLT) has anti-gonadal effect by inhibiting gonadotropin release in vertebrates. Serotonin is the precursor of MLT biochemically derived from tryptophan. Serotonin could regulate neuron activity and improve sleeping quality, making people calm, and happy. Both MLT and serotonin might inhibit testosterone (T) release. Whereas the action mechanisms of MLT and serotonin on T production by Leydig cells are still unclear. Our aim was to investigate the direct effects and action mechanisms of MLT and serotonin on T release. Leydig cells were prepared from adult male rats by continuous percoll gradient method. MLT at concentrations of 10^(-8)-10^(-6) M inhibited basal release of T after pre-incubation of MLT for 1 h. Besides, after pre-incubation with MLT (10^(-8)-10^(-6) M) for 1 h, the human chorionic gonadotropin (hCG)-evoked T release was significantly inhibited by the co-incubation of MLT (10^(-8)-10^(-6) M) in vitro. Although serotonin had similar effects, in contrast, tryptophan had no effect on the steroidogenesis in rat Leydig cells. Furthermore, MLT at 10^(-7) M and 10^(-6) M inhibited forskolin- and 8-Br-cAMP-evoked release of T in vitro by rat Leydig cells. MLT at 10^(-8) M also significantly inhibited T release in response to androstenedione. Serotonin had weak effects on T release in response to forskolin and 8-Br-cAMP androstenedione in vitro as compared with MLT. These results suggested that both MLT and serotonin inhibited T release in rat Leydig cells via cAMP-associated pathway and the reduced activity of 17-ketoreductase.