Document Detail


In vitro studies on the role of the peripheral-type benzodiazepine receptor in steroidogenesis.
MedLine Citation:
PMID:  10418986     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
M Culty; H Li; N Boujrad; H Amri; B Vidic; J M Bernassau; J L Reversat; V Papadopoulos
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.; Review    
Journal Detail:
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:
Created Date:  1999-08-02     Completed Date:  1999-08-02     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9015483     Medline TA:  J Steroid Biochem Mol Biol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  123-30     Citation Subset:  IM    
Affiliation:
Department of Cell Biology, Georgetown University Medical Center, Washington, DC 20007, USA.
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MeSH Terms
Descriptor/Qualifier:
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:
K04-HD-01031/HD/NICHD NIH HHS; R01-ES-07747/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Chorionic Gonadotropin; 0/Receptors, GABA-A; 0/Recombinant Proteins; 0/Steroids

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