Trichostatin A reduces GnRH mRNA expression with a concomitant increase in retinaldehyde dehydrogenase in GnRH-producing neurons

• Trichostatin A (TSA) decreased GnRH mRNA expression in GT1-7 cells.
• TSA increased RALDH, a retinoic acid(RA)-synthesizing enzyme.
• RA stimulation significantly reduced GnRH mRNA expression in these cells.
• Pan-RA receptor inverse agonist and RA metabolism inhibitor did not modulate the effect of TSA.

Trichostatin A (TSA) is a selective inhibitor of mammalian histone deacetylase and is widely used to modify the ability of DNA transcription factors to bind DNA within chromatin by interfering with histone deacetylation. In the GnRH-producing neuronal cell line GT1-7, TSA significantly reduced expression of GnRH mRNA. Kisspeptin, a known regulator of GnRH release, failed to increase GnRH mRNA expression and did not modify TSA-induced reduction of GnRH expression. TSA, but not kisspeptin, increased histone acetylation in whole-cell lysates and significantly stimulated the expression of retinaldehyde dehydrogenase (RALDH), a retinoic acid (RA)-synthesizing enzyme that is known to be involved in cell differentiation. In addition, treatment of the GT1-7 cells with RA dose-dependently inhibited the expression of GnRH mRNA. Whereas, TSA-induced reduction of GnRH mRNA was not modulated by treatment with the pan-RA receptor inverse agonist BMS493 or the RA metabolism inhibitor liarozole.Our current results suggest that the RALDH and RA might not be directly involved in the reduction of GnRH expression induced by TSA, however these substances could be a novel regulator of GnRH.