**7. Trichostatin A, a selective inhibitor of mammalian histone deacetylase, reduces GnRH expression in GT1-7 cells**

Observations from the studies using GT1-7 cells and primary cultures of fetal rat brain imply that kisspeptin could affect GnRH neurons and increase GnRH expression. In addition, kisspeptin may change the GT1-7 cells' expression levels of Kiss1R. GnRH synthesis is not only regulated by kisspeptin, but several experimental reagents can modify the GnRH synthesis in GnRH-producing cells. Trichostatin A (TSA), a selective inhibitor of histone deacetylase, is an experimental reagent that modifies gene expression by opening chromatin structure through hyperacetylation of histones [32]. The structural change in chromatin allows transcription factors to bind DNA to modify gene expression. In GnRH-producing GT1-7 cells, TSA significantly reduced GnRH expression, with a concomitant increase in the gene encoding retinaldehyde dehydrogenase, which catalyzes the oxidation of retinol to retinoic acid [33]. Because retinoic acid also reduces GnRH expression in these cells, epigenetic mechanisms modified through retinaldehyde dehydrogenase, and retinoic acid might have an inhibitory effect on GnRH production (**Figure 1**).
