Increased transcription and increased messenger ribonucleic acid (mRNA) stability contribute to increased GATA6 mRNA abundance in polycystic ovary syndrome theca cells.
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.
Ho
Clement K M
CK
Center for Research on Reproduction and Women's Health, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Wood
Jennifer R
JR
Stewart
Douglas R
DR
Ewens
Kathryn
K
Ankener
Wendy
W
Wickenheisser
Jessica
J
Nelson-Degrave
Velen
V
Zhang
Zhibing
Z
Legro
Richard S
RS
Dunaif
Andrea
A
McAllister
Jan M
JM
Spielman
Richard
R
Strauss
Jerome F
JF
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
D004274:DNA, Recombinant; D050993:GATA6 Transcription Factor; C494759:GATA6 protein, human; D020033:Protein Isoforms; D012333:RNA, Messenger