Source:http://linkedlifedata.com/resource/pubmed/id/16926195
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
Pt 18
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| pubmed:dateCreated |
2006-9-8
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| pubmed:abstractText |
Oocytes regulate follicle growth by secreting paracrine growth factors that act on neighbouring granulosa cells (GCs). Those factors identified to date are mainly members of the transforming growth factor-beta (TGFbeta) superfamily, but little is known about which specific receptor/signalling system(s) they employ. This study was conducted to determine the requisite pathways utilised by oocytes to promote GC proliferation. We used an established oocyte-secreted mitogen bioassay, where denuded mouse oocytes are co-cultured with mural GCs. Oocytes, growth differentiation factor-9 (GDF9), TGFbeta1 and activin-A all promoted GC DNA synthesis, but bone-morphogenetic protein 6 (BMP6) did not. Subsequently, we tested the capacity of various TGFbeta superfamily receptor ectodomains (ECD) to neutralise oocyte- or specific growth factor-stimulated GC proliferation. The BMP type-II receptor (BMPR-II) ECD antagonised oocyte and GDF9 bioactivity dose-dependently, but had no or minimal effect on TGFbeta1 and activin-A bioactivity, demonstrating its specificity. The TGFbetaR-II, activinR-IIA and activinR-IIB ECDs all failed to neutralise oocyte- or GDF9-stimulated GC DNA synthesis, whereas they did antagonise the activity of their respective native ligands. An activin receptor-like kinase (ALK) 4/5/7 inhibitor, SB431542, also antagonised both oocyte and GDF9 bioactivity in a dose-dependent manner. Consistent with these findings, oocytes, GDF9 and TGFbeta1 all activated SMAD2/3 reporter constructs in transfected GC, and led to phosphorylation of SMAD2 proteins in treated cells. Surprisingly, oocytes did not activate the SMAD1/5/8 pathway in transfected GCs although exogenous BMP6 did. This study indicates that oocyte paracrine factors primarily utilise a similar signalling pathway first identified for GDF9 that employs an unusual combination of TGFbeta superfamily receptors, the BMPR-II and a SMAD2/3 stimulatory ALK (4, 5 or 7), for transmitting their mitogenic actions in GC. This cell-signalling pathway may also have relevance in the hypothalamic-pituitary axis and in germ-somatic cell interactions in the testis.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Activins,
http://linkedlifedata.com/resource/pubmed/chemical/Bmp15 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Bmp6 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Protein 15,
http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Protein 6,
http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Gdf9 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Growth Differentiation Factor 9,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Smad2 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Smad3 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta
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| pubmed:status |
MEDLINE
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| pubmed:month |
Sep
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| pubmed:issn |
0021-9533
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
15
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| pubmed:volume |
119
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
3811-21
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:16926195-Activins,
pubmed-meshheading:16926195-Animals,
pubmed-meshheading:16926195-Bone Morphogenetic Protein 15,
pubmed-meshheading:16926195-Bone Morphogenetic Protein 6,
pubmed-meshheading:16926195-Bone Morphogenetic Protein Receptors, Type II,
pubmed-meshheading:16926195-Bone Morphogenetic Proteins,
pubmed-meshheading:16926195-Cell Proliferation,
pubmed-meshheading:16926195-DNA,
pubmed-meshheading:16926195-Female,
pubmed-meshheading:16926195-Gene Expression Regulation,
pubmed-meshheading:16926195-Granulosa Cells,
pubmed-meshheading:16926195-Growth Differentiation Factor 9,
pubmed-meshheading:16926195-Intercellular Signaling Peptides and Proteins,
pubmed-meshheading:16926195-Mice,
pubmed-meshheading:16926195-Oocytes,
pubmed-meshheading:16926195-Paracrine Communication,
pubmed-meshheading:16926195-RNA, Messenger,
pubmed-meshheading:16926195-Signal Transduction,
pubmed-meshheading:16926195-Smad2 Protein,
pubmed-meshheading:16926195-Smad3 Protein,
pubmed-meshheading:16926195-Transforming Growth Factor beta
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| pubmed:year |
2006
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| pubmed:articleTitle |
Molecular basis of oocyte-paracrine signalling that promotes granulosa cell proliferation.
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| pubmed:affiliation |
Research Centre for Reproductive Health, Discipline of Obstetrics and Gynaecology, The Queen Elizabeth Hospital, University of Adelaide, Australia. robert.gilchrist@adelaide.edu.au
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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