title: Hormonal coordination of natriuretic peptide type C and natriuretic peptide receptor 3 expression in mouse granulosa cells.
abstract: Natriuretic peptide type C (NPPC) and its receptor natriuretic peptide receptor 2 (NPR2) regulate cGMP in ovarian follicles and participate in maintaining oocyte meiotic arrest. We investigated the regulation of Nppc expression in mouse granulosa cells in vivo and in vitro. In mural granulosa cells (MGCs) in vivo, eCG caused an increase in Nppc mRNA, and subsequent human chorionic gonadotropin (hCG) treatment caused a decrease. A culture system was established for MGCs isolated from follicles not stimulated with equine chorionic gonadotropin to further define the mechanisms controlling Nppc expression. In this system, expression of Nppc mRNA was increased by estradiol (E2), with augmentation by follicle-stimulating hormone (FSH), but FSH or luteinizing hormone (LH) alone had no effect. Thus, estrogens are important for regulating Nppc expression, probably by feedback mechanisms enhancing the action of gonadotropins. In MGCs treated with E2 plus FSH in vitro, subsequent treatment with EGF, but not LH, decreased Nppc mRNA. MGCs express higher levels of both Nppc and Lhcgr mRNAs than cumulus cells. Oocyte-derived paracrine factors suppressed cumulus cell Lhcgr but not Nppc expression. Thus, higher Nppc expression by MGCs is not the result of oocyte suppression of expression in cumulus cells. Another possible regulator of the LH-induced NPPC decrease is NPR3, an NPPC clearance receptor. Human chorionic gonadotropin increased Npr3 expression in vivo and LH increased Npr3 mRNA in cultured MGCs, independently of EGF receptor activation. Interestingly, despite the increase in Npr3 mRNA, the hCG-induced decrease in ovarian NPPC occurred normally in an Npr3 mutant (lgj), thus NPR3 probably does not participate in regulation of ovarian NPPC levels or oocyte development.
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME 04609, USA.
authors.forename: Kyung-Bon
authors.initials: KB
authors.lastname: Lee
authors.forename: Meijia
authors.initials: M
authors.lastname: Zhang
authors.forename: Koji
authors.initials: K
authors.lastname: Sugiura
authors.forename: Karen
authors.initials: K
authors.lastname: Wigglesworth
authors.forename: Tracy
authors.initials: T
authors.lastname: Uliasz
authors.forename: Laurinda A
authors.initials: LA
authors.lastname: Jaffe
authors.forename: John J
authors.initials: JJ
authors.lastname: Eppig
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000502:physiology; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D006107:Granulosa Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007986:Luteinizing Hormone / Q000494:pharmacology*; D051379:Mice; D008817:Mice, Mutant Strains; D023421:Models, Animal; D009154:Mutation / Q000235:genetics; D020098:Natriuretic Peptide, C-Type / Q000235:genetics / Q000378:metabolism*; D009865:Oocytes / Q000166:cytology; D012333:RNA, Messenger / Q000378:metabolism; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D006063:Chorionic Gonadotropin; D012333:RNA, Messenger; D020098:Natriuretic Peptide, C-Type; D004958:Estradiol; D004815:Epidermal Growth Factor; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D017461:Receptors, Atrial Natriuretic Factor; C073616:atrial natriuretic factor receptor C; D006152:Cyclic GMP