title: Trichostatin A reduces GnRH mRNA expression with a concomitant increase in retinaldehyde dehydrogenase in GnRH-producing neurons.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane 693-8501, Japan. Electronic address: kanasaki@med.shimane-u.ac.jp.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Kanasaki
authors.affiliation: Department of Obstetrics and Gynecology, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane 693-8501, Japan.
authors.forename: Tselmeg
authors.initials: T
authors.lastname: Mijiddorj
authors.affiliation: Department of Obstetrics and Gynecology, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane 693-8501, Japan.
authors.forename: Unurjargal
authors.initials: U
authors.lastname: Sukhbaatar
authors.affiliation: Department of Obstetrics and Gynecology, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane 693-8501, Japan.
authors.forename: Aki
authors.initials: A
authors.lastname: Oride
authors.affiliation: Department of Obstetrics and Gynecology, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane 693-8501, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ishihara
authors.affiliation: Department of Obstetrics and Gynecology, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane 693-8501, Japan.
authors.forename: Ikuko
authors.initials: I
authors.lastname: Yamagami
authors.affiliation: Department of Obstetrics and Gynecology, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane 693-8501, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Kyo
mesh_terms: D000818:Animals; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D007987:Gonadotropin-Releasing Hormone / Q000096:biosynthesis*; D006877:Hydroxamic Acids / Q000494:pharmacology*; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D050697:Retinal Dehydrogenase / Q000096:biosynthesis*
chemical_list: D006877:Hydroxamic Acids; D007987:Gonadotropin-Releasing Hormone; C012589:trichostatin A; D050697:Retinal Dehydrogenase
keywords: GnRH; Kisspeptin; RALDH; Retinoic acid; Trichostatin A