The molecular signature of polycystic ovary syndrome (PCOS) theca cells defined by gene expression profiling

Jennifer R Wood, Clement K.M. Ho, Velen L. Nelson-Degrave, Jan M. McAllister, Jerome F. Strauss

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

Polycystic ovary syndrome (PCOS) is characterized by increased ovarian androgen secretion, anovulatory infertility due to arrested folliculogenesis, and is frequently found in association with insulin resistance and obesity. Characterization of PCOS theca cells demonstrated that elevated expression of the steroidogenic enzymes 17α hydroxylase/17,20 lyase (CYP17) and P450 side chain cleavage enzyme (CYP11A1) play a role in increased androgen production by 3β-hydroxysteroid dehydrogenase in the PCOS theca cell. However, the gene networks and signal transduction pathways which cause the altered expansion of the steroid enzymes remain to be determined. In order to identify these gene networks and/or signaling pathways, we carried out global gene expression profiling of normal and PCOS theca cells using subtractive suppressive hybridization and oligonucleotide microarray analysis. These analyses demonstrated that approximately 2% of genes expressed in the theca cell exhibit altered mRNA abundance in PCOS. Characterization of these genes revealed that retinoic acid synthesis and Wnt signal transduction are altered in the PCOS theca cell. In addition, the transcription factor GATA6, which regulates the promoter activity of CYP17 and CYP11A, was increased in the PCOS compared to normal theca cells. Thus, global gene expression profiling has identified potential pathways which may determine the PCOS theca cell phenotype.

Original languageEnglish (US)
Pages (from-to)51-60
Number of pages10
JournalJournal of Reproductive Immunology
Volume63
Issue number1
DOIs
StatePublished - Aug 1 2004

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Theca Cells
Polycystic Ovary Syndrome
Gene Expression Profiling
Steroid 17-alpha-Hydroxylase
Gene Regulatory Networks
Androgens
GATA6 Transcription Factor
Signal Transduction
Enzymes
3-Hydroxysteroid Dehydrogenases
Cholesterol Side-Chain Cleavage Enzyme
Microarray Analysis
Mixed Function Oxygenases
Tretinoin
Oligonucleotide Array Sequence Analysis
Infertility
Genes
Insulin Resistance
Obesity
Steroids

Keywords

  • GATA6
  • Microarray analysis
  • Polycystic ovary syndrome
  • Retinoic acid
  • Wnt signal transduction

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Reproductive Medicine
  • Obstetrics and Gynecology

Cite this

The molecular signature of polycystic ovary syndrome (PCOS) theca cells defined by gene expression profiling. / Wood, Jennifer R; Ho, Clement K.M.; Nelson-Degrave, Velen L.; McAllister, Jan M.; Strauss, Jerome F.

In: Journal of Reproductive Immunology, Vol. 63, No. 1, 01.08.2004, p. 51-60.

Research output: Contribution to journalArticle

Wood, Jennifer R ; Ho, Clement K.M. ; Nelson-Degrave, Velen L. ; McAllister, Jan M. ; Strauss, Jerome F. / The molecular signature of polycystic ovary syndrome (PCOS) theca cells defined by gene expression profiling. In: Journal of Reproductive Immunology. 2004 ; Vol. 63, No. 1. pp. 51-60.
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