Altered endothelin expression in granulosa-lutein cells of women with polycystic ovary syndrome

Abstract

AimsTo examine the levels of endothelin system components in granulosa lutein cells (GLCs) of women with PCOS and compare them to normally ovulating women undergoing In Vitro Fertilization (IVF).Polycystic ovary syndrome (PCOS) is one of the most common endocrine-metabolic disorders in women of reproductive age. Endothelins are locally produced by endothelial and granulosa cells of the preovulatory follicle. Abnormal expression or production of endothelins may be a contributing factor in PCOS pathogenesis. Main methodsFollicular aspirates containing GLCs were obtained from PCOS and normally ovulating patients undergoing oocyte retrieval during the IVF cycle. RNA was extracted and endothelin system components were quantified using real-time PCR. GLCs were cultured in basal media for 7days, and then challenged with various luteinizing agents (luteinizing hormone, hCG, or forskolin) for 24h. Key findingsIn GLCs from women with PCOS, Endothelin-1 mRNA expression was elevated (2.2-fold) as compared with normally ovulating women, whereas endothelin-2 mRNA was reduced (1.8-fold). ET receptors and endothelin-converting enzyme showed the same expression levels in the two groups. In vitro modeling showed that although the steroidogenic response was preserved in GLC, endothelin expression levels were not exhibited in vitro in their original pattern. SignificanceDysregulation of ovarian endothelin expression may induce a pathologic ovulation pattern characteristic of PCOS.