title: The glycan structure in recombinant human FSH affects endocrine activity and global gene expression in human granulosa cells.
abstract: The aim of this study was to analyse the biological response to different recombinant human FSH (rhFSH) glycosylation variants on the endocrine activity and gene expression at whole-genome scale in human granulosa-like tumor cell line, KGN. The effects of differences in rhFSH sialylation and oligosaccharide complexity were determined on steroid hormone and inhibin production. A microarray approach was used to explore gene expression patterns induced by rhFSH glycosylation variants. Set enrichment analysis revealed that hormone sialylation and oligosaccharide complexity in rhFSH differentially affected the expression of genes involved in essential biological processes and molecular functions of KGN cells. The relevance of rhFSH oligosaccharide structure on steroidogenesis was confirmed assessing gene expression by real time-PCR. The results demonstrate that FSH oligosaccharide structure affects expression of genes encoding proteins, growth factors and hormones essential for granulosa cells function.
authors.affiliation: Centro de Investigaciones Endocrinológicas (CEDIE/CONICET), Hospital de Niños Ricardo Gutiérrez, Gallo No. 1330, C1425EFB Ciudad Autónoma de Buenos Aires, Argentina. nloreti@cedie.org.ar
authors.forename: Nazareth
authors.initials: N
authors.lastname: Loreti
authors.forename: Cristobal
authors.initials: C
authors.lastname: Fresno
authors.forename: David
authors.initials: D
authors.lastname: Barrera
authors.forename: Luz
authors.initials: L
authors.lastname: Andreone
authors.forename: Saúl Lira
authors.initials: SL
authors.lastname: Albarran
authors.forename: Elmer Andrés
authors.initials: EA
authors.lastname: Fernandez
authors.forename: Fernando
authors.initials: F
authors.lastname: Larrea
authors.forename: Stella
authors.initials: S
authors.lastname: Campo
mesh_terms: D045744:Cell Line, Tumor; D004703:Endocrine System / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D043373:Follicle Stimulating Hormone, Human / Q000737:chemistry* / Q000494:pharmacology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D053263:Gene Regulatory Networks / Q000235:genetics; D006031:Glycosylation / Q000187:drug effects; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007265:Inhibins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011134:Polysaccharides / Q000737:chemistry* / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000737:chemistry*; D013256:Steroids / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D043373:Follicle Stimulating Hormone, Human; D011134:Polysaccharides; D011994:Recombinant Proteins; D013256:Steroids; D007265:Inhibins