@article{3095971,
    title = "Effect of peroxisome proliferators on Leydig cell peripheral-type benzodiazepine receptor gene expression, hormone-stimulated cholesterol transport, and steroidogenesis: Role of the peroxisome proliferator-activator receptor α",
    author = "Gazouli, M. and Yao, Z.-X. and Boujrad, N. and Christopher Corton, J. and Culty, M. and Papadopoulos, V.",
    journal = "FRONTIERS IN ENDOCRINOLOGY",
    year = "2002",
    volume = "143",
    number = "7",
    pages = "2571-2583",
    publisher = "Japan Endocrine Society",
    doi = "10.1210/endo.143.7.8895",
    keywords = "benzodiazepine receptor;  peroxisome proliferator;  peroxisome proliferator activated receptor alpha;  transcription factor, animal cell;  article;  cell function;  cell proliferation;  cholesterol transport;  gene expression regulation;  Leydig cell;  lipid metabolism;  liver carcinogenesis;  mitochondrial membrane;  mouse;  nonhuman;  priority journal;  protein family;  receptor gene;  seminiferous tubule;  steroidogenesis;  testosterone release;  transcription regulation",
    abstract = "In this study, we hypothesized that many of the reported effects of phthalate esters and other peroxisome proliferators (PPs) in the testis are mediated by members of the PP-activated receptor (PPAR) family of transcription factors through alterations in proteins involved in steroidogenesis. Exposure of Leydig cells to PPs prevented cholesterol transport into the mitochondria after hormonal stimulation and inhibited steroid synthesis, without altering total cell protein synthesis or mitochondrial and DNA integrity. PPs also reduced the levels of the cholesterol-binding protein peripheral-type benzodiazepine receptor (PBR) because of a direct transcriptional inhibition of PBR gene expression in MA-10 Leydig cells. MA-10 cells contain mRNAs for PPARα and PPARβ/δ, but not for PPARγ. In vivo treatment of mice with PPs resulted in the reduction of both testis PBR mRNA and circulating testosterone levels, in agreement with the proposed role of PBR in steroidogenesis. By contrast, liver PBR mRNA levels were increased, in agreement with the proposed role of PBR in cell growth/tumor formation in nonsteroidogenic tissues. However, PPs did not inhibit testosterone production and testis PBR expression in PPARα-null mice. These results suggest that the antiandrogenic effect of PPs is mediated by a PPARα-dependent inhibition of Leydig cell PBR gene expression."
}