Effects of valproate on steroid production and correlative steroidogenesis enzyme mRNA in human luteinized granulose cells / 中国药理学通报

ABSTRACT

AIM Valproate (VPA) is widely used to treat epilepsy. Long-term treatment of women with VPA has been reported to be associated with a PCOS-like syndrome. The aim of the present study was to investigate the effects of clinically relevant concentrations of valproate on steroidogenesis and steroidogenesis acute regulatory protein (StAR),cholesterol side-chain cleavage enzyme (P450scc)and cytochrome P450 aromatase (P450arom) mRNA expression in human luteinized granulosa cells in vitro. METHODS Human luteinized granulosa cells were isolated from oocyte retrieval of in vitro fertilization procedure and were cultured with DMEM medium and treated with various concentrations of valproate (0, 100, 250 mg?L -1), the culture media was collected after 2 days for progesterone and estradiol measurements by standard radiommunoassay, StAR, P450scc and P450arom mRNA in granulose cells were detected by fluorescent real-time RT-PCR (TaqMan assay). RESULTS Valproate caused significant increase of progesterone (P