title: Growth differentiation factor 9 promotes rat preantral follicle growth by up-regulating follicular androgen biosynthesis.
abstract: The transition from preantral to early antral stage is the penultimate stage of ovarian follicular development in terms of gonadotropin dependence and follicle destiny. Although oocyte-somatic cell communication is important in early follicular development, our knowledge of the precise role of the oocyte-derived growth differentiation factor (GDF)-9 during preantral follicle growth is incomplete. We examined whether and by what means oocyte-derived GDF-9 controls follicular development and steroidogenesis during the preantral to early antral transition, by a combination of in vitro gene manipulation (i.e. intraoocyte injection of GDF-9 antisense oligos) and preantral follicle culture. Intraoocyte injection of GDF-9 antisense suppressed rat preantral follicle growth in vitro, whereas GDF-9 enhanced follicular development. GDF-9 augmented testosterone production in preantral follicles. GDF-9 antisense suppressed androgen production and CYP17A1 mRNA expression in cultured follicles, a response attenuated by exogenous GDF-9. The nonaromatizable androgen 5alpha-dihydrotestosterone rescued the follicular growth arrest caused by GDF-9 down-regulation. The specific androgen receptor antagonist flutamide suppressed GDF-9-induced preantral follicle growth in vitro. The data suggest that GDF-9 plays an important role in promoting preantral follicle growth by up-regulating follicular androgen biosynthesis. GDF-9 is essential for CYP17A1 expression during follicular development from the preantral to the early antral stage.
authors.affiliation: Department of Obstetrics and Gynaecology, Reproductive Biology Unit and Division of Reproductive Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Makoto
authors.initials: M
authors.lastname: Orisaka
authors.forename: Jin-Yi
authors.initials: JY
authors.lastname: Jiang
authors.forename: Sanae
authors.initials: S
authors.lastname: Orisaka
authors.forename: Fumikazu
authors.initials: F
authors.lastname: Kotsuji
authors.forename: Benjamin K
authors.initials: BK
authors.lastname: Tsang
mesh_terms: D000728:Androgens / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism / Q000494:pharmacology; D055429:Growth Differentiation Factor 9 / Q000235:genetics / Q000502:physiology*; D008845:Microinjections; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000494:pharmacology; D009865:Oocytes / Q000187:drug effects; D006080:Ovarian Follicle / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
chemical_list: D000728:Androgens; D055429:Growth Differentiation Factor 9; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D013739:Testosterone; D005640:Follicle Stimulating Hormone; D013254:Steroid 17-alpha-Hydroxylase