Inhibitory effect of melatonin on testosterone synthesis is mediated via GATA-4/SF-1 transcription factors

The aim of the present study was to elucidate whether the GATA-4/SF-1 signalling pathway is involved in the inhibitory effects of melatonin on testosterone production in both the TM3 Leydig cell line and in C57BL/6J mice. In-vitro experiments demonstrated that melatonin treatment significantly reduced testosterone levels in cell culture medium ( P < 0.05 or P < 0.01); and decreased intracellular cyclic adenosine monophospha accumulation ( P < 0.05 or P < 0.01) and mRNA/protein expression of GATA-4 , SF-1 (NR5A1) , StAR , P450SCC (CYP11A1) and 3β-HSD ( P < 0.05 or P < 0.01). These effects were blocked by N-acetyl-2-benzyltryptamin, a melatonin receptor antagonist . Similar effects of melatonin on testosterone production ( P < 0.05 or P < 0.01) and down-regulation of transcription factors GATA-4 and SF-1 ( P < 0.01) were also observed in mice treated with intratesticular injections of melatonin. Overall, the data suggest that the inhibitory effects of melatonin on testosterone production are mediated via down-regulation of GATA-4 and SF-1 expression.