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

• Published in: Journal of reproductive immunology 2004-08, Vol.63 (1), p.51-60
• Main Authors: Wood, Jennifer R, Ho, Clement K.M, Nelson-Degrave, Velen L, McAllister, Jan M, Strauss, Jerome F
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cells, Cultured; Female; Female genital diseases; GATA6; Gene Expression Profiling - methods; Gynecology. Andrology. Obstetrics; Humans; In Situ Hybridization; Medical sciences; Microarray analysis; Non tumoral diseases; Oligonucleotide Array Sequence Analysis; Polycystic ovary syndrome; Polycystic Ovary Syndrome - genetics; Reproducibility of Results; Retinoic acid; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Sensitivity and Specificity; Signal Transduction - genetics; Theca Cells - physiology; Wnt signal transduction
• ISSN: 0165-0378; 1872-7603
• DOI: 10.1016/j.jri.2004.01.010

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.