Melatonin inhibits the expression of steroidogenic acute regulatory protein and steroidogenesis in MA-10 cells

The effects of melatonin on steroidogenesis and steroidogenic acute regulat ory (StAR) protein expression were investigated in MA-IO mouse Leydig tumor cells. MA-10 cells were treated with human chorionic gonadotropin/cyclic a denosine monophosphate (hCG/cAMP) analogue alone or with hCG/cAMP analogue plus melatonin in different dosages (0.1 nM to 10 muM). Steroid production and the expression of StAR protein were measured. Melatonin directly inhibi ted hCG- or dbcAMP-stimulated progesterone production in MA-10 cells within 3 hours. The inhibitory effects of melatonin on hCG- or dbcAMP-stimulated steroid production in MA-10 cells were abolished by a comparative melatonin receptor antagonist, luzindole. 22R-hydroxycholesterol reversed melatonin' s inhibitory effects, which illustrated that melatonin did not suppress P45 0(scc) enzyme activity. Moreover, StAR protein expression stimulated by hCG and dbcAMP was maximally reduced by 10 nM of melatonin treatment for 3 hou rs. The effects of prolonged exposure (12 h) to melatonin with dbcAMP stimu lation in MA-10 cells were also examined. The expression of StAR protein an d steroid production were reduced by melatonin concentrations from 1 nM to 10 muM. However, melatonin at a dose of 1 nM had no effect in 3-hour treatm ent. Our results indicate that melatonin suppressed MA-10 mouse Leydig cell steroidogenesis through specific binding sites by blocking StAR protein ex pression without altering the activity of P450(scc) enzyme.