Document Detail

Activin A reduces luteinisation of human luteinised granulosa cells and has opposing effects to human chorionic gonadotropin in vitro.
MedLine Citation:
PMID:  18710903     Owner:  NLM     Status:  MEDLINE    
The transition of the dominant follicle into the corpus luteum is of fundamental reproductive importance. Luteinisation involves disparate changes in the gene expression of follicular granulosa cells that differentiate into the granulosa-lutein cells of the corpus luteum after the gonadotrophin surge. We have shown that activin and human chorionic gonadotropin (hCG) have opposing effects during luteolysis. Therefore, we hypothesised that activin A was an inhibitor of luteinisation that was blocked during the pre-ovulatory gonadotrophin surge. Ovarian tissue and cells were collected from women with regular cycles having hysterectomy and women undergoing oocyte retrieval for assisted conception. Genes that changes during luteinisation were investigated in primary cultures of luteinised granulosa cells exposed to activin A and hCG in vitro. hCG promotes a luteinised granulosa cell phenotype, while activin A promotes a more follicular phenotype in luteinised cells by upregulating granulosa cells markers such as FSHR, HSD11B2 and downregulating LHCGR. In addition, activin A blocked hCG upregulation of STAR, HSD3B1 and HSD11B1 and downregulation of oestrogen receptor alpha. Activin A antagonised hCG effects in a dose-dependent manner and could block the hCG-stimulated molecular inhibitors of activin action (inhibin alpha-subunit, follistatin and TGFBR3). These studies show that hCG and activin A have opposing effects on luteinised granulosa cells and some effects of activin are seen only in the presence of hCG. While hCG can inhibit activin action in granulosa cells to facilitate luteinisation, activin A can promote an unluteinised phenotype in luteinised granulosa cells. This confirms the importance of adequate activin withdrawal during luteinisation in women.
Michelle Myers; Sander van den Driesche; Alan S McNeilly; W Colin Duncan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-08-18
Journal Detail:
Title:  The Journal of endocrinology     Volume:  199     ISSN:  1479-6805     ISO Abbreviation:  J. Endocrinol.     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-10-28     Completed Date:  2009-07-10     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  0375363     Medline TA:  J Endocrinol     Country:  England    
Other Details:
Languages:  eng     Pagination:  201-12     Citation Subset:  IM    
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MeSH Terms
11-beta-Hydroxysteroid Dehydrogenase Type 1 / metabolism
11-beta-Hydroxysteroid Dehydrogenase Type 2 / metabolism
Activins / pharmacology*
Cells, Cultured
Chorionic Gonadotropin / pharmacology*
Dose-Response Relationship, Drug
Estrogen Receptor alpha / metabolism
Luteal Cells / drug effects*,  metabolism*
Luteinization / drug effects
Middle Aged
Progesterone / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Grant Support
MC_U127685843//Medical Research Council
Reg. No./Substance:
0/Chorionic Gonadotropin; 0/Estrogen Receptor alpha; 0/activin A; 0/estrogen receptor alpha, human; 104625-48-1/Activins; 4G7DS2Q64Y/Progesterone; EC Dehydrogenase Type 1; EC Dehydrogenase Type 2; EC protein, human; EC protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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