Introduction: Polycystic ovary syndrome (PCOS) is a common endocrinopathy in premenopausal women and is associated with hyperandrogenism, anovulatory infertility, and metabolic abnormalities. Abnormalities in the steroidogenic pathway of both theca and granulosa cells have previously been reported, but there has been no comprehensive analysis of steroidogenic gene expression in granulosa-lutein (GL) cells of women with PCOS. In this study, we investigated a panel of genes involved in steroid synthesis, metabolism and action in GL cells of women with PCOS compared to women with normal ovaries and regular cycles.
Methods: Granulosa cells were collected during IVF from women with and without PCOS. RNA was extracted, cDNA synthesised and quantitative PCR used to screen 19 genes. Expression data was also correlated to the FSH dose used for superovulation. Further, we examined the effects of FSH or the androgen dihydrotestosterone (DHT) on expression profiles in cultured GL cells to determine whether any differences observed could be attributed to the direct actions of FSH or androgen.
Results/discussion: The majority of steroidogenic genes were unchanged in GL cells of women with anovulatory PCOS, but CYP11A1 expression was significantly decreased (threefold, P<0.01). However, the most significant differences were seen in genes involved in oestrogen action. SULT1E1 (encoding oestrogen sulfotransferase) was significantly increased sevenfold (P<0.001), with similar results found in ovulatory women with polycystic ovary morphology. In addition, expression of ESR1 and ESR2 (encoding ERα and ERβ) was increased threefold (P<0.05). Preliminary in-vitro studies showed that SULT1E1 expression is not altered by FSH but is upregulated by DHT treatment.
These results are the first to show that genes involved both in oestrogen metabolism and action are differentially expressed in ovarian cells from women with PCOS. It remains to be determined what the significance of these findings is in the aetiology of reproductive dysfunction in PCOS.
11 Jul 2016 - 11 Jul 2016