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Cited by 219

The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.

Targeted Disruption of the Peripheral-type Benzodiazepine Receptor Gene Inhibits Steroidogenesis in the R2C Leydig Tumor Cell Line

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Papadopoulos, Vassilios, Amri, Hakima, Li, Hua, Boujrad, Noureddine, Vidic, Branislav, Garnier, Martine·1997·Journal of Biological Chemistry

Abstract

To evaluate the role of the mitochondrial peripheral-type benzodiazepine receptor (PBR) in steroidogenesis, we developed a molecular approach based on the disruption of the PBR gene, by homologous recombination, in the constitutive steroid producing R2C rat Leydig tumor cell line. Inactivation of one allele of the PBR gene resulted in the suppression of PBR mRNA and ligand binding expression. Immunoblot and electron microscopic immunogold labeling analyses confirmed the absence of the 18-kDa PBR protein in the selected clone. Although mitochondria from the PBR-negative cells contained high levels of the constitutively expressed 30-kDa steroidogenic activity regulator protein, these cells produced minimal amounts of steroids compared with normal cells (5%). Moreover, mitochondria from PBR-negative cells failed to produce pregnenolone when supplied with exogenous cholesterol. Addition of the hydrosoluble cholesterol derivative, 22R-hydroxycholesterol, increased steroid production by the PBR-negative R2C cells, indicating that the cholesterol transport mechanism was impaired. Stable transfection of the PBR-negative R2C Leydig cells with a vector containing the PBR cDNA resulted in the recovery of the steroidogenic function of the cells. These data demonstrate that PBR is an indispensable element of the steroidogenic machinery, where it mediates the delivery of the substrate cholesterol to the inner mitochondrial side chain cleavage cytochrome P-450.

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Metadata

Authors
Papadopoulos, V., Amri, H., Li, H., Boujrad, N., Vidic, B., & Garnier, M.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1997-12
Volume
272
Issue
51
Pages
32129-32135
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2134397312
Cited by
219
References
8
FWCI
3.49
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Targeted Disruption of the Peripheral-type Benzodiazepine Receptor Gene Inhibits Steroidogenesis in the R2C Leydig Tumor Cell Line. https://app.cochat.ai/papers/10.1074/jbc.272.51.32129
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Papadopoulos, V., Amri, H., Li, H., Boujrad, N., Vidic, B., & Garnier, M. (1997). Targeted Disruption of the Peripheral-type Benzodiazepine Receptor Gene Inhibits Steroidogenesis in the R2C Leydig Tumor Cell Line. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.272.51.32129

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