| In vitro studies on the role of the peripheral-type benzodiazepine receptor in steroidogenesis. | |
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MedLine Citation:
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PMID: 10418986 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In vitro studies using isolated cells, mitochondria and submitochondrial fractions demonstrated that in steroid synthesizing cells, the peripheral-type benzodiazepine receptor (PBR) is an outer mitochondrial membrane protein, preferentially located in the outer/inner membrane contact sites, involved in the regulation of cholesterol transport from the outer to the inner mitochondrial membrane, the rate-determining step in steroid biosynthesis. Mitochondrial PBR ligand binding characteristics and topography are sensitive to hormone treatment suggesting a role of PBR in the regulation of hormone-mediated steroidogenesis. Targeted disruption of the PBR gene in Leydig cells in vitro resulted in the arrest of cholesterol transport into mitochondria and steroid formation; transfection of the mutant cells with a PBR cDNA rescued steroidogenesis demonstrating an obligatory role for PBR in cholesterol transport. Molecular modeling of PBR suggested that it might function as a channel for cholesterol. This hypothesis was tested in a bacterial system devoid of PBR and cholesterol. Cholesterol uptake and transport by these cells was induced upon PBR expression. Amino acid deletion followed by site-directed mutagenesis studies and expression of mutant PBRs demonstrated the presence in the cytoplasmic carboxy-terminus of the receptor of a cholesterol recognition/interaction amino acid consensus sequence. This amino acid sequence may help for recruiting the cholesterol coming from intracellular sites to the mitochondria. |
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Authors:
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M Culty; H Li; N Boujrad; H Amri; B Vidic; J M Bernassau; J L Reversat; V Papadopoulos |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S.; Review |
Journal Detail:
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Title: The Journal of steroid biochemistry and molecular biology Volume: 69 ISSN: 0960-0760 ISO Abbreviation: J. Steroid Biochem. Mol. Biol. Publication Date: 1999 Apr-Jun |
Date Detail:
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Created Date: 1999-08-02 Completed Date: 1999-08-02 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 9015483 Medline TA: J Steroid Biochem Mol Biol Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 123-30 Citation Subset: IM |
Affiliation:
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Department of Cell Biology, Georgetown University Medical Center, Washington, DC 20007, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Chorionic Gonadotropin / physiology Escherichia coli / genetics Leydig Cells / metabolism Male Receptors, GABA-A / genetics, metabolism, physiology* Recombinant Proteins / genetics, metabolism Steroids / biosynthesis* |
| Grant Support | |
ID/Acronym/Agency:
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K04-HD-01031/HD/NICHD NIH HHS; R01-ES-07747/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Chorionic Gonadotropin; 0/Receptors, GABA-A; 0/Recombinant Proteins; 0/Steroids |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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