Background: Polycystic Ovarian Syndrome (PCOS) is a complex endocrine and reproductive disorder affecting approximately 10% of women of reproductive age. Hallmarks include hyperandrogenism, ovulatory dysfunction and insulin resistance, with PCOS women at an increased risk for Type 2 Diabetes. Paeoniflorin, the major constituent in Radix Albus Paeoniae Lactiflorae, is commonly used in Chinese medicine for the treatment of metabolic and reproductive disorders however the molecular mechanisms in which Paeoniflorin benefits to PCOS have not yet been defined.
Aims: To examine the effects of Paeoniflorin on testosterone and progesterone secretion in dexamethasone-induced cellular model of PCOS and to define the molecular mechanisms involved.
Methods: Primary murine theca cells were isolated from ovaries of 4-week-old mice and treated with concentrations of Paeoniflorin extract (1-100 µg/mL) in the presence of dexamethasone (10 µM). After 24h treatment, culture media was collected for immunoassay of testosterone and progesterone. Total protein was then extracted for western blot analysis of key steroidogenic enzymes, cholesterol side-chain cleavage (CYP11A1) and 17α-hydroxylase (CYP17A1). Cells were also fixed on coverslips for immunefluorescent staining with CYP11A1 and CYP17A1 antibodies. qRT-PCR was used to reveal mRNA expression in the cells with and without Paeoniflorin treatment.
Results: Dexamethasone significantly increased testosterone and decreaed progesterone compared to control cells (p<0.05) and therefore emulated hyperandrogenism and ovulatory dysfunction in PCOS. Interestingly, Paeoniflorin (100µg/mL) significantly deceased testosterone in dexamethasone treated theca cells and increased progesterone (p<0.05). Protein expression of CYP11A1 but not CYP17A1 was significantly decreased in Paeoniflorin treated cells (100µg/mL) in both Western blot analysis and immunofluorescent staining (p<0.05).
Conclusions: Paeoniflorin reduces testosterone secretion in theca cells which appears to be through suppression of CYP11A1 that regulates the rate-limiting step in the ovarian steroidogenic pathway. These findings suggest that the herb may be useful in targeting hyperandrogenism in the treatment of PCOS with further experiments warranted.