title: Syndecan 1 represses cell growth and FSH responsiveness in human granulosa cells.
abstract: Albeit devoid of intrinsic catalytic activity, the transmembrane heparan sulphate proteoglycan syndecan 1 plays critical roles in cellular processes such as extracellular matrix crosstalk, cytoskeletal organization, cell spreading, proliferation and differentiation. During the ovarian cycle, the expression of syndecan 1 in granulosa cells shows cyclic variation suggesting that it might fulfil specific roles in follicle development. To investigate its physiological roles on granulosa cells, syndecan 1 was overexpressed in human granulosa cell line KGN which retains features of granulosa cells from small antral follicle such as estradiol (E2) synthesis and low expression of functional FSH receptor (FSHR). We demonstrated that overexpression of syndecan 1 in immature granulosa cells (KGN-SDC1) induces a profound alteration in their intrinsic characteristics including enhanced spreading and attachment, both associated with a reduced growth rate. Flow cytometry analysis revealed that syndecan 1 overexpression increases the percentage of KGN cells in quiescent phase. This partial cell cycle exit is concordant with downregulated levels ofCCND1andCDK4and upregulated expression of CDK inhibitorCDKN1AIn parallel both unstimulated and FSH-induced E2 synthesis are reduced in KGN-SDC1 through both repression ofCYP19A1andFSHRmRNA associated with decreased levels of potential regulatorsNR5A1andESR2Additionally, we provide evidence that transient cAMP accumulation reduction in cells overexpressing syndecan 1 is accompanied by an increase in cAMP-hydrolysing PDE activity. Our results demonstrated that syndecan 1 might regulate differentiation of granulosa cells and follicular development by means of various mechanisms involving morphological changes, control of signalling pathways and alterations in gene expressions.Free French abstract: A French translation of this abstract is freely available at http://www.reproduction-online.org/content/153/6/797/suppl/DC1.Reproduction.
authors.affiliation: OestrogènesReproduction, Cancer, Normandie Université, UNICAEN, Normandie, France.
authors.forename: Simon
authors.initials: S
authors.lastname: Colombe
authors.affiliation: OestrogènesReproduction, Cancer, Normandie Université, UNICAEN, Normandie, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Houllier
authors.affiliation: OestrogènesReproduction, Cancer, Normandie Université, UNICAEN, Normandie, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Fleurot
authors.affiliation: OestrogènesReproduction, Cancer, Normandie Université, UNICAEN, Normandie, France.|CHU de CaenService d'Anatomie Pathologique, Caen, France.
authors.forename: Guénaëlle
authors.initials: G
authors.lastname: Levallet
authors.affiliation: OestrogènesReproduction, Cancer, Normandie Université, UNICAEN, Normandie, France.|CHU de CaenLaboratoire de Fécondation In Vitro, Service de Gynécologie Obstétrique, Caen, France.
authors.forename: Annie
authors.initials: A
authors.lastname: Benhaïm
authors.affiliation: OestrogènesReproduction, Cancer, Normandie Université, UNICAEN, Normandie, France.
authors.forename: Pierre-Jacques
authors.initials: PJ
authors.lastname: Bonnamy
authors.affiliation: OestrogènesReproduction, Cancer, Normandie Université, UNICAEN, Normandie, France Jerome.levallet@unicaen.fr.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Levallet
mesh_terms: D001141:Aromatase / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006106:Granulosa Cell Tumor / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008875:Middle Aged; D011962:Receptors, FSH / Q000378:metabolism; D015398:Signal Transduction; D053668:Syndecan-1 / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D011962:Receptors, FSH; D053668:Syndecan-1; D005640:Follicle Stimulating Hormone; D001141:Aromatase; C561410:CYP19A1 protein, human