Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of human theca cells from women with polycystic ovary syndrome and normal theca cells treated with valproate


ABSTRACT: Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder that affects 5-10% of reproductive aged women. The hallmark characteristic of PCOS is increased ovarian androgen synthesis. Previous studies by our laboratory demonstrated that increased androgen synthesis is a stable biochemical phenotype of PCOS theca cells which are the primary source of ovarian androgen production. The increase in theca cell steroidogenesis was due to an increase in expression of several steroidogenic enzymes including CYP17 and CYP11A but not StAR. Interestingly, the anti-epileptic drug valproic acid induces increased theca cell androgen synthesis and increased CYP17 and CYP11A mRNA levels. In this study we have characterized the gene expression profiles of theca cells obtained from normal or polycystic ovaries which were maintained in the absence (UNT) or presence (VPA) of valproic acid. The data identifed new candidate genes and novel signaling pathways which may contribute to the manifestation of PCOS phenotypes including increased androgen production. The experiments in this study were carried using the Affymetrix U133A and U133B oligonucleotide chips.

ORGANISM(S): Homo sapiens

SUBMITTER: Jennifer Rebecca Wood 

PROVIDER: E-GEOD-1615 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Valproate-induced alterations in human theca cell gene expression: clues to the association between valproate use and metabolic side effects.

Wood Jennifer R JR   Nelson-Degrave Velen L VL   Jansen Erik E   McAllister Jan M JM   Mosselman Sietse S   Strauss Jerome F JF  

Physiological genomics 20041214 3


Valproic acid (VPA) is an anti-epileptic drug that has been associated with polycystic ovary syndrome (PCOS)-like symptoms, including increased ovarian androgen production. The hyperandrogenemia likely reflects the stimulatory action of VPA on theca cell androgen synthesis and has been correlated to its activity as a histone deacteylase inhibitor in these cells. To determine whether VPA induces a PCOS-like genomic phenotype, we compared the gene expression profiles of untreated (UNT) normal, VPA  ...[more]

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