SFEBES2016 Oral Communications Neuroendocrinology and Reproduction (6 abstracts)
Dysregulation of the steroidogenic gene network in granulosa cells from women with PCOS
A Lerner 1 , M Coates 1 , J Velupillai 1 , G Christopoulos 2 , M Liyanage 2 , R Islam 2 , S Lavery 2 , V Tsui 1 , K Hardy 1 & S Franks 1
1Imperial College London, London, UK; 2Imperial College Healthcare NHS Trust, London, UK.
Polycystic ovary syndrome (PCOS) is a common endocrinopathy that is associated with anovulatory infertility, menstrual disturbances as well as an adverse metabolic profile. Although the pathophysiology of PCOS remains unclear, dysregulation of gene expression has been previously shown in theca and granulosa cells (GC). However, there has been no comprehensive analysis of steroidogenic gene expression in GCs from women with PCOS. In this study, we performed a comprehensive gene expression analysis of the steroidogenic network in human GCs. GCs were retrieved during egg collection for in-vitro fertilisation from women with (1) normal ovaries and regular cycles (2) PCO with regular, ovulatory cycles (ovPCO) and (3) anovulatory PCOS (anovPCO). Quantitative PCR was used to analyse changes in gene expression. Cultured GCs were used to investigate direct effects of the androgen dihydrotestosterone (DHT) on steroidogenic gene expression. Finally, using Mapper2 software we searched for putative androgen response elements (AREs) in the promoters of genes involved in steroid synthesis and metabolism. We found that CYP11a1 was significant decreased (3-fold, P<0.01) in GCs of both ovPCO and anovPCO. However, the biggest change was seen in estrogen sulfotransferase (SULT1e1) expression that was strongly upregulated (7-fold, P<0.001) in both ovPCO and anovPCO. In the light of this, genes encoding ERα and ERβ were investigated, the expression of which was also shown to be significantly increased (3-fold, P<0.05). Interestingly, we identified several putative AREs in the promotors of CYP11a1, SULT1e1, ERα and ERβ supporting the notation of direct regulation by androgen receptor binding. Furthermore, preliminary in-vitro studies showed that SULT1e1 expression is directly upregulated by DHT treatment. In summary we show differential expression between GCs from women with and without PCO, of genes implicated in estrogen action and metabolism and suggest that these may be, at least in part, a function of androgen action.
Volume 44
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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