title: Increased transcription and increased messenger ribonucleic acid (mRNA) stability contribute to increased GATA6 mRNA abundance in polycystic ovary syndrome theca cells.
abstract: BACKGROUND
  Polycystic ovary syndrome (PCOS) theca cells secrete increased levels of androgens. The mRNA and protein levels of the transcription factor GATA6, which regulates expression of several steroidogenic enzymes, are increased in PCOS theca cells. Thus, GATA6 is a PCOS candidate gene.
  
  
  OBJECTIVE
  The objective of the study was to explore mechanisms by which GATA6 mRNA levels are increased in PCOS theca cells.
  
  
  METHODS
  Theca cell cDNA and genomic DNA from normal individuals and PCOS patients were subjected to quantitative RT-PCR and sequence analysis, respectively.
  
  
  METHODS
  The experiments were performed in a university laboratory.
  
  
  METHODS
  Four hundred sixty-nine families that contain at least one PCOS patient were ascertained for genetic studies. Theca cells were obtained from four normal individuals and four PCOS patients.
  
  
  RESULTS
  Nascent GATA6 transcript levels, which reflect GATA6 gene transcription, were significantly increased in PCOS theca cells. In normal theca cells, GATA6 mRNA has a short half-life, which was attributed to an AU-rich 3'-untranslated region sequence. The half-life of GATA6 transcripts was also significantly longer in the PCOS theca cells. However, no sequence variations in the GATA6 gene locus were associated with PCOS.
  
  
  CONCLUSIONS
  In PCOS theca cells, GATA6 gene transcription and the stability of the GATA6 mRNA are increased. Because there is no sequence variation in the GATA6 gene locus, which is associated with PCOS, it is likely that the increased gene transcription and mRNA stability are due to intrinsic differences in PCOS theca cells.
authors.affiliation: Center for Research on Reproduction and Women's Health, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
authors.forename: Clement K M
authors.initials: CK
authors.lastname: Ho
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Wood
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Stewart
authors.forename: Kathryn
authors.initials: K
authors.lastname: Ewens
authors.forename: Wendy
authors.initials: W
authors.lastname: Ankener
authors.forename: Jessica
authors.initials: J
authors.lastname: Wickenheisser
authors.forename: Velen
authors.initials: V
authors.lastname: Nelson-Degrave
authors.forename: Zhibing
authors.initials: Z
authors.lastname: Zhang
authors.forename: Richard S
authors.initials: RS
authors.lastname: Legro
authors.forename: Andrea
authors.initials: A
authors.lastname: Dunaif
authors.forename: Jan M
authors.initials: JM
authors.lastname: McAllister
authors.forename: Richard
authors.initials: R
authors.lastname: Spielman
authors.forename: Jerome F
authors.initials: JF
authors.lastname: Strauss
mesh_terms: D001483:Base Sequence; D002478:Cells, Cultured; D004274:DNA, Recombinant; D005260:Female; D050993:GATA6 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D014644:Genetic Variation; D006801:Humans; D008969:Molecular Sequence Data; D011085:Polycystic Ovary Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016133:Polymerase Chain Reaction / Q000379:methods; D020033:Protein Isoforms / Q000378:metabolism; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D013799:Theca Cells / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D004274:DNA, Recombinant; D050993:GATA6 Transcription Factor; C494759:GATA6 protein, human; D020033:Protein Isoforms; D012333:RNA, Messenger