Expression of genes controlling steroid metabolism and action in granulosalutein cells of women with polycystic ovaries
File(s)Lerner et al 2019 MCE.pdf (7.49 MB)
Accepted version
Author(s)
Type
Journal Article
Abstract
Introduction
Aberrant function of granulosa cells has been implicated in the pathophysiology of PCOS.
Materials & methods
Granulosa lutein (GL) cells were collected during oocyte retrieval for IVF/ICSI. RT-qPCR was used to compare gene expression between 12 control women, 12 with ovulatory PCO and 12 with anovulatory PCOS. To examine which genes are directly regulated by androgens, GL cells from an additional 12 control women were treated in-vitro with 10 nM dihydrotestosterone (DHT).
Results
GL cells from women with PCOS showed reduced expression of CYP11A1 3-fold (p = 0.005), HSD17B1 1.8-fold (p = 0.02) and increased expression of SULT1E1 7-fold (p = 0.0003). Similar results were seen in ovulatory women with PCO. GL cells treated with 10 nM DHT showed a 4-fold (p = 0.03) increase in expression of SULT1E1 and a 5-fold reduction in SRD5A1 (p = 0.03).
Conclusions
These findings support the notion that aberrant regulation of steroid metabolism or action play a part in ovarian dysfunction in PCOS.
Aberrant function of granulosa cells has been implicated in the pathophysiology of PCOS.
Materials & methods
Granulosa lutein (GL) cells were collected during oocyte retrieval for IVF/ICSI. RT-qPCR was used to compare gene expression between 12 control women, 12 with ovulatory PCO and 12 with anovulatory PCOS. To examine which genes are directly regulated by androgens, GL cells from an additional 12 control women were treated in-vitro with 10 nM dihydrotestosterone (DHT).
Results
GL cells from women with PCOS showed reduced expression of CYP11A1 3-fold (p = 0.005), HSD17B1 1.8-fold (p = 0.02) and increased expression of SULT1E1 7-fold (p = 0.0003). Similar results were seen in ovulatory women with PCO. GL cells treated with 10 nM DHT showed a 4-fold (p = 0.03) increase in expression of SULT1E1 and a 5-fold reduction in SRD5A1 (p = 0.03).
Conclusions
These findings support the notion that aberrant regulation of steroid metabolism or action play a part in ovarian dysfunction in PCOS.
Date Issued
2019-04-15
Date Acceptance
2019-02-18
Citation
Molecular and Cellular Endocrinology, 2019, 486, pp.47-54
ISSN
0303-7207
Publisher
Elsevier
Start Page
47
End Page
54
Journal / Book Title
Molecular and Cellular Endocrinology
Volume
486
Copyright Statement
© 2019 Elsevier Ltd. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/.
Sponsor
Medical Research Council (MRC)
Wellbeing of Women
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000461360500006&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
G0802782
RG1853
Subjects
Science & Technology
Life Sciences & Biomedicine
Cell Biology
Endocrinology & Metabolism
PCOS
Granulosa cells
Steroidogenic enzymes
FOLLICLE-STIMULATING-HORMONE
RAT 17-BETA-HYDROXYSTEROID-DEHYDROGENASE TYPE-1
DEHYDROEPIANDROSTERONE-SULFATE
DIAGNOSTIC-CRITERIA
ANDROGEN PRODUCTION
ANOVULATORY WOMEN
CYP11A1
GROWTH
POLYMORPHISMS
GONADOTROPINS
Publication Status
Published
Date Publish Online
2019-02-22