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

Reprod Biomed Online. 2015 Nov;31(5):638-46. doi: 10.1016/j.rbmo.2015.07.009. Epub 2015 Aug 7.

Abstract

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.

Keywords: GATA-4; Leydig cell; SF-1; melatonin; restosterone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cyclic AMP / metabolism
  • Down-Regulation / drug effects
  • GATA4 Transcription Factor / metabolism*
  • Leydig Cells / drug effects*
  • Leydig Cells / metabolism
  • Male
  • Melatonin / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Signal Transduction / drug effects*
  • Steroidogenic Factor 1 / metabolism*
  • Testosterone / biosynthesis*

Substances

  • GATA4 Transcription Factor
  • Steroidogenic Factor 1
  • Testosterone
  • Cyclic AMP
  • Melatonin