title: The localization and regulation of proprotein convertase subtilisin/kexin (PCSK) 6 in human ovary.
abstract: OBJECTIVE
  The aim of this study is to evaluate the expression and regulation of proprotein convertase subtilisin/kexin (PCSK) 6, which is known to be an important factor in the production of bone morphogenetic protein (BMP) cytokines in human ovary.
  
  
  METHODS
  The localization of PCSK 6 protein in normal human ovaries was examined by immunohistochemistry. Human granulosa cells (GC), obtained from 34 patients undergoing ovarian stimulation for in vitro fertilization, were cultured with BMP-2, BMP-6, BMP-7, BMP-15, growth differentiation factor (GDF)-9, and activin-A with or without FSH. PCSK 6 mRNA expression level was evaluated by quantitative real-time reverse transcription and polymerase chain reaction (RT-PCR).
  
  
  RESULTS
  An immunohistochemistry study revealed that GC expressed PCSK 6 throughout follicular development, beginning in the primary follicle stage, while oocytes expressed PCSK 6 from the primordial follicle stage onwards. An in vitro study demonstrated that BMP-2, BMP-6, BMP-7, and BMP-15, not activin-A and GDF-9, decreased PCSK 6 gene expression in human GC. FSH induced PCSK 6 mRNA in the presence of activin-A or GDF-9. GDF-3, which is an inhibitor of BMP cytokines, also induced PCSK 6 mRNA expression.
  
  
  CONCLUSIONS
  PCSK 6, which is a critical factor to produce BMP cytokines, was suppressed with BMP stimulation in human GC, suggesting the presence of a negative feedback system in the follicular development process.
authors.affiliation: Department of Obstetrics and Gynecology, University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Ikumi
authors.initials: I
authors.lastname: Akiyama
authors.forename: Osamu
authors.initials: O
authors.lastname: Yoshino
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Osuga
authors.forename: Jia
authors.initials: J
authors.lastname: Shi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hirota
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hirata
authors.forename: Miyuki
authors.initials: M
authors.lastname: Harada
authors.forename: Kaori
authors.initials: K
authors.lastname: Koga
authors.forename: Akihisa
authors.initials: A
authors.lastname: Fujimoto
authors.forename: Tetsu
authors.initials: T
authors.lastname: Yano
authors.forename: Yuji
authors.initials: Y
authors.lastname: Taketani
mesh_terms: D028341:Activins / Q000494:pharmacology*; D000328:Adult; D019485:Bone Morphogenetic Proteins / Q000096:biosynthesis / Q000494:pharmacology*; D002478:Cells, Cultured; D005260:Female; D005498:Follicular Phase; D006107:Granulosa Cells / Q000201:enzymology; D055429:Growth Differentiation Factor 9 / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D006080:Ovarian Follicle / Q000201:enzymology / Q000254:growth & development; D010053:Ovary / Q000201:enzymology*; D043484:Proprotein Convertases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*
chemical_list: D019485:Bone Morphogenetic Proteins; D055429:Growth Differentiation Factor 9; D012333:RNA, Messenger; D028341:Activins; C080654:PCSK6 protein, human; D043484:Proprotein Convertases; D012697:Serine Endopeptidases