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


METHODS
Follicular 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 7 days, and then challenged with various luteinizing agents (luteinizing hormone, hCG, or forskolin) for 24 h.


RESULTS
In 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.


CONCLUSIONS
Dysregulation of ovarian endothelin expression may induce a pathologic ovulation pattern characteristic of PCOS.
IVF Unit, Department of Obstetrics & Gynecology, Hadassah Hebrew University Medical Center, Mt. Scopus, Jerusalem, Israel. talim@hadassah.org.il
Tal
T
Imbar
Eyal
E
Klipper
Caryn
C
Greenfield
Arye
A
Hurwitz
Ronit
R
Haimov-Kochman
Rina
R
Meidan
D000328:Adult; D016282:Aspartic Acid Endopeptidases / Q000235:genetics; D016022:Case-Control Studies; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D019332:Endothelin-1 / Q000235:genetics*; D019333:Endothelin-2 / Q000235:genetics*; D000072396:Endothelin-Converting Enzymes; D005260:Female; D005307:Fertilization in Vitro; D005786:Gene Expression Regulation; D006801:Humans; D008184:Luteal Cells / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000494:pharmacology; D008666:Metalloendopeptidases / Q000235:genetics; D054315:Oocyte Retrieval; D011085:Polycystic Ovary Syndrome / Q000503:physiopathology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D017466:Receptors, Endothelin / Q000235:genetics; D013997:Time Factors; D055815:Young Adult
D006063:Chorionic Gonadotropin; D019332:Endothelin-1; D019333:Endothelin-2; D012333:RNA, Messenger; D017466:Receptors, Endothelin; D005576:Colforsin; D007986:Luteinizing Hormone; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes