title: Molecular Plasticity of Male and Female Murine Gonadotropes Revealed by mRNA Sequencing.
abstract: Gonadotropes in the anterior pituitary gland are of particular importance within the hypothalamic-pituitary-gonadal axis because they provide a means of communication and thus a functional link between the brain and the gonads. Recent results indicate that female gonadotropes may be organized in the form of a network that shows plasticity and adapts to the altered endocrine conditions of different physiological states. However, little is known about functional changes on the molecular level within gonadotropes during these different conditions. In this study we capitalize on a binary genetic strategy in order to fluorescently label murine gonadotrope cells. Using this mouse model allows to produce an enriched gonadotrope population using fluorescence activated cell sorting to perform mRNA sequencing. By using this strategy, we analyze and compare the expression profile of murine gonadotropes in different genders and developmental and hormonal stages. We find that gonadotropes taken from juvenile males and females, from cycling females at diestrus and at proestrus, from lactating females, and from adult males each have unique gene expression patterns with approximately 100 to approximately 500 genes expressed only in one particular stage. We also demonstrate extensive gene-expression profile changes with up to approximately 2200 differentially expressed genes when comparing female and male development, juveniles and adults, and cycling females. Differentially expressed genes were significantly enriched in the GnRH signaling, calcium signaling, and MAPK signaling pathways by Kyoto Encyclopedia of Genes and Genomes analysis. Our data provide an unprecedented molecular view of the primary gonadotropes and reveal a high degree of molecular plasticity within the gonadotrope population.
authors.affiliation: Department of Pharmacology and Toxicology (S.Q., L.M., U.B.) and Center for Integrative Physiology and Molecular Medicine (E.K.), University of Saarland School of Medicine, Kirrberger Straße D-66421 Homburg, Germany; and Department of Genetics (K.N., G.G., S.T., J.W.), University of Saarland, D-66123 Saarbrücken, Germany.
authors.forename: Sen
authors.initials: S
authors.lastname: Qiao
authors.affiliation: Department of Pharmacology and Toxicology (S.Q., L.M., U.B.) and Center for Integrative Physiology and Molecular Medicine (E.K.), University of Saarland School of Medicine, Kirrberger Straße D-66421 Homburg, Germany; and Department of Genetics (K.N., G.G., S.T., J.W.), University of Saarland, D-66123 Saarbrücken, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Nordström
authors.affiliation: Department of Pharmacology and Toxicology (S.Q., L.M., U.B.) and Center for Integrative Physiology and Molecular Medicine (E.K.), University of Saarland School of Medicine, Kirrberger Straße D-66421 Homburg, Germany; and Department of Genetics (K.N., G.G., S.T., J.W.), University of Saarland, D-66123 Saarbrücken, Germany.
authors.forename: Leon
authors.initials: L
authors.lastname: Muijs
authors.affiliation: Department of Pharmacology and Toxicology (S.Q., L.M., U.B.) and Center for Integrative Physiology and Molecular Medicine (E.K.), University of Saarland School of Medicine, Kirrberger Straße D-66421 Homburg, Germany; and Department of Genetics (K.N., G.G., S.T., J.W.), University of Saarland, D-66123 Saarbrücken, Germany.
authors.forename: Gilles
authors.initials: G
authors.lastname: Gasparoni
authors.affiliation: Department of Pharmacology and Toxicology (S.Q., L.M., U.B.) and Center for Integrative Physiology and Molecular Medicine (E.K.), University of Saarland School of Medicine, Kirrberger Straße D-66421 Homburg, Germany; and Department of Genetics (K.N., G.G., S.T., J.W.), University of Saarland, D-66123 Saarbrücken, Germany.
authors.forename: Sascha
authors.initials: S
authors.lastname: Tierling
authors.affiliation: Department of Pharmacology and Toxicology (S.Q., L.M., U.B.) and Center for Integrative Physiology and Molecular Medicine (E.K.), University of Saarland School of Medicine, Kirrberger Straße D-66421 Homburg, Germany; and Department of Genetics (K.N., G.G., S.T., J.W.), University of Saarland, D-66123 Saarbrücken, Germany.
authors.forename: Elmar
authors.initials: E
authors.lastname: Krause
authors.affiliation: Department of Pharmacology and Toxicology (S.Q., L.M., U.B.) and Center for Integrative Physiology and Molecular Medicine (E.K.), University of Saarland School of Medicine, Kirrberger Straße D-66421 Homburg, Germany; and Department of Genetics (K.N., G.G., S.T., J.W.), University of Saarland, D-66123 Saarbrücken, Germany.
authors.forename: Jörn
authors.initials: J
authors.lastname: Walter
authors.affiliation: Department of Pharmacology and Toxicology (S.Q., L.M., U.B.) and Center for Integrative Physiology and Molecular Medicine (E.K.), University of Saarland School of Medicine, Kirrberger Straße D-66421 Homburg, Germany; and Department of Genetics (K.N., G.G., S.T., J.W.), University of Saarland, D-66123 Saarbrücken, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Boehm
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000235:genetics; D000066670:Cell Plasticity / Q000235:genetics*; D004031:Diestrus / Q000235:genetics / Q000378:metabolism; D030762:Estrous Cycle / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D052681:Gonadotrophs / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D007774:Lactation / Q000235:genetics* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D051379:Mice; D011359:Proestrus / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics*; D017423:Sequence Analysis, RNA; D012741:Sexual Maturation / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D059467:Transcriptome
chemical_list: D012333:RNA, Messenger; D007987:Gonadotropin-Releasing Hormone