title: Transcriptional repression of the Ahr gene by LHCGR signaling in preovulatory granulosa cells is controlled by chromatin accessibility.
abstract: Recent advances in establishing the role of the aryl hydrocarbon receptor (Ahr) in normophysiology have discovered its fundamental role, amongst others, in female reproduction. Considering previous studies suggesting the hormonal modulation of Ahr, we aimed to investigate whether in murine granulosa cells (GCs) the gonadotropins regulate Ahr expression and how this is mechanistically implemented. We found that the FSH-like substance--pregnant mare serum gonadotropin--led to stimulation of Ahr expression. More importantly hCG produced relatively rapid reduction of Ahr mRNA in GCs of preovulatory follicles. We show for the first time that LHCGR signaling in regulating the Ahr message involves protein kinase A pathway and is attributable to decreased transcription rate. Finally, we found that Ahr promoter accessibility was decreased by hCG, implicating chromatin remodeling in Ahr gene regulation by LH.
authors.affiliation: Department of Cell Biology, Institute of Molecular and Cell Biology, University of Tartu, Riia 23, 51010 Tartu, Estonia.
authors.forename: Indrek
authors.initials: I
authors.lastname: Teino
authors.affiliation: Department of Cell Biology, Institute of Molecular and Cell Biology, University of Tartu, Riia 23, 51010 Tartu, Estonia.
authors.forename: Antti
authors.initials: A
authors.lastname: Matvere
authors.affiliation: Department of Cell Biology, Institute of Molecular and Cell Biology, University of Tartu, Riia 23, 51010 Tartu, Estonia.
authors.forename: Sulev
authors.initials: S
authors.lastname: Kuuse
authors.affiliation: Department of Cell Biology, Institute of Molecular and Cell Biology, University of Tartu, Riia 23, 51010 Tartu, Estonia.
authors.forename: Sulev
authors.initials: S
authors.lastname: Ingerpuu
authors.affiliation: Department of Cell Biology, Institute of Molecular and Cell Biology, University of Tartu, Riia 23, 51010 Tartu, Estonia.
authors.forename: Toivo
authors.initials: T
authors.lastname: Maimets
authors.affiliation: Department of Cell Biology, Institute of Molecular and Cell Biology, University of Tartu, Riia 23, 51010 Tartu, Estonia.
authors.forename: Arnold
authors.initials: A
authors.lastname: Kristjuhan
authors.affiliation: Department of Cell Biology, Institute of Molecular and Cell Biology, University of Tartu, Riia 23, 51010 Tartu, Estonia. Electronic address: tarmo.tiido@ut.ee.
authors.forename: Tarmo
authors.initials: T
authors.lastname: Tiido
mesh_terms: D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D002843:Chromatin / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005498:Follicular Phase / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D006736:Horses; D006801:Humans; D051379:Mice; D008954:Models, Biological; D011247:Pregnancy; D014176:Protein Biosynthesis / Q000187:drug effects; D020871:RNA Stability / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics* / Q000378:metabolism; D011974:Receptors, LH / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D006063:Chorionic Gonadotropin; D002843:Chromatin; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D011974:Receptors, LH; D012097:Repressor Proteins; D017868:Cyclic AMP-Dependent Protein Kinases
keywords: 2,3,7,8-tetrachlorodibenzo-p-dioxin; ActD; Ahr; Aryl hydrocarbon receptor; CHART-PCR; CHX; Chromatin structure; FSK; Granulosa cells; HDAC; LHCGR signaling; Ovary reproduction; TCDD; TSA; TSS; Transcription regulation; acinomycin D; aryl hydrocarbon receptor; chromatin accessibility by real-time PCR; cycloheximide; forskolin; heteronuclear RNA; histone deacetylase; hnRNA; transcriptional start site; trichostatin A