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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2004-6-7
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pubmed:abstractText |
Steroidogenic acute regulatory protein (StAR) plays a critical role in the initial step of steroid hormone synthesis. In the present study, we investigated the role of liver receptor homolog-1 (LRH-1) and dosage-sensitive sex reversal, adrenal hypoplasia congenital critical region on the X chromosome, gene 1 (DAX-1) in the regulation of StAR gene expression in human granulosa cell tumor cells. We also examined the effect of protein kinase A (PKA) signaling pathway on the expression of StAR in the presence of LRH-1 and DAX-1. Cell transfection, mutation analysis, and EMSA were performed. LRH-1 significantly induced StAR promoter activity in a concentration-dependent manner. This induction was further augmented in the presence of PKA agonist. Using deletion analysis, we demonstrated LRH-1 binding site at -105/-95. Mutation of this site resulted in a significant decrease in the StAR promoter activity. Using EMSA, the ability of this cis-element to bind LRH-1 was confirmed. DAX-1 inhibited LRH-1-stimulated StAR promoter activity in a concentration-dependent manner. This inhibition was also maintained in the presence of PKA stimulation. Our results demonstrated that LRH-1 plays a critical role in the induction of StAR gene expression. We hypothesize that LRH-1 could be the major transcription factor responsible for the rapid and significant increase in ovarian StAR gene expression after ovulation.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/DAX-1 Orphan Nuclear Receptor,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NR0B1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Nr0b1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Nr5a2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Retinoic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/steroidogenic acute regulatory...
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0021-972X
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
89
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3042-7
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15181096-Cell Line, Tumor,
pubmed-meshheading:15181096-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:15181096-DAX-1 Orphan Nuclear Receptor,
pubmed-meshheading:15181096-DNA-Binding Proteins,
pubmed-meshheading:15181096-Electrophoretic Mobility Shift Assay,
pubmed-meshheading:15181096-Female,
pubmed-meshheading:15181096-Gene Expression,
pubmed-meshheading:15181096-Granulosa Cell Tumor,
pubmed-meshheading:15181096-Humans,
pubmed-meshheading:15181096-Ovarian Neoplasms,
pubmed-meshheading:15181096-Ovary,
pubmed-meshheading:15181096-Ovulation,
pubmed-meshheading:15181096-Phosphoproteins,
pubmed-meshheading:15181096-Promoter Regions, Genetic,
pubmed-meshheading:15181096-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:15181096-Receptors, Retinoic Acid,
pubmed-meshheading:15181096-Repressor Proteins,
pubmed-meshheading:15181096-Signal Transduction
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pubmed:year |
2004
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pubmed:articleTitle |
Liver receptor homolog-1 regulates the expression of steroidogenic acute regulatory protein in human granulosa cells.
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pubmed:affiliation |
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9032, USA.
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pubmed:publicationType |
Journal Article
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