Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2004-12-13
pubmed:abstractText
We have recently reported that bone morphogenetic protein-4 (BMP-4) can inhibit progesterone production by ovine granulosa cells (GCs). Here, we have investigated the underlying mechanisms of this effect in basal as well as in FSH-induced conditions. We have confirmed that treatment with BMP-4 decreased basal GC progesterone secretion and totally abolished FSH-stimulating action. This inhibitory action was associated with a decrease in the expression of cAMP-regulated genes, steroidogenic acute regulatory protein (StAR) and P450 side-chain cleavage (P450 scc) at mRNA and protein levels. However, BMP-4 did not alter basal cAMP production by GCs. In contrast, BMP-4 decreased by half the FSH-induced cAMP production and strongly inhibited cAMP-induced progesterone production. Thus, the inhibitory effect of BMP-4 was exerted both upstream and downstream of cAMP signalling. We next examined the downstream effect, focusing on cAMP-dependent transcription factors, steroidogenic factor-1 (SF-1) and CREB, through the BMP factor signalling intermediary, Smad1. As expected, BMP-4 induced phosphorylation and transcriptional activity of Smad1 in ovine GCs. BMP-4-activated Smad1 did not affect CREB activity but inhibited the transcriptional activity of SF-1 on the canonical SF-1 responsive element. Interestingly, this transcriptional inhibitory mechanism occurred on transfected StAR and P450 scc promoter. Based on these results, we propose that SF-1 is a key target in the inhibitory mechanism exerted by BMP-4 on progesterone synthesis by ovine GCs in culture. Because SF-1 plays an essential role in the differentiation of GCs, our findings could have new implications in understanding the role of BMP family members in the control of ovarian folliculogenesis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/BMP4 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Bmp4 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Protein 4, http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP, http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Follicle Stimulating Hormone, http://linkedlifedata.com/resource/pubmed/chemical/NR5A1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Progesterone, http://linkedlifedata.com/resource/pubmed/chemical/SMAD1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Smad Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Smad1 Protein, http://linkedlifedata.com/resource/pubmed/chemical/Smad1 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Steroidogenic Factor 1, http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators, http://linkedlifedata.com/resource/pubmed/chemical/steroidogenic factor 1, mouse
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0952-5041
pubmed:author
pubmed:issnType
Print
pubmed:volume
33
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
805-17
pubmed:dateRevised
2009-8-12
pubmed:meshHeading
pubmed-meshheading:15591037-Animals, pubmed-meshheading:15591037-Bone Morphogenetic Protein 4, pubmed-meshheading:15591037-Bone Morphogenetic Proteins, pubmed-meshheading:15591037-Cells, Cultured, pubmed-meshheading:15591037-Cyclic AMP, pubmed-meshheading:15591037-DNA-Binding Proteins, pubmed-meshheading:15591037-Female, pubmed-meshheading:15591037-Follicle Stimulating Hormone, pubmed-meshheading:15591037-Gene Expression Regulation, pubmed-meshheading:15591037-Granulosa Cells, pubmed-meshheading:15591037-Humans, pubmed-meshheading:15591037-Mice, pubmed-meshheading:15591037-Progesterone, pubmed-meshheading:15591037-Sheep, pubmed-meshheading:15591037-Signal Transduction, pubmed-meshheading:15591037-Smad Proteins, pubmed-meshheading:15591037-Smad1 Protein, pubmed-meshheading:15591037-Steroidogenic Factor 1, pubmed-meshheading:15591037-Swine, pubmed-meshheading:15591037-Trans-Activators, pubmed-meshheading:15591037-Transcription, Genetic
pubmed:year
2004
pubmed:articleTitle
Molecular basis of bone morphogenetic protein-4 inhibitory action on progesterone secretion by ovine granulosa cells.
pubmed:affiliation
Physiologie de la Reproduction et des Comportements, UMR 6175 INRA-CNRS-Université de Tours, Haras Nationaux, 37380 Nouzilly, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't