Mitochondrial peripheral-type benzodiazepine receptor expression. Correlation with gonadotropin-releasing hormone (GnRH) agonist-induced apoptosis in the corpus luteum.
We have demonstrated that continuous administration of a gonadotropin-releasing hormone agonist (GnRH-Ag) decreases the expression of the mitochondrial peripheral-type benzodiazepine receptor (PBR) and increases the rate of DNA degradation in a time-dependent manner in the corpora lutea of pregnant rats. In the present study, we show in situ the GnRH-Ag-induced DNA fragmentation and correlate the increase of the rate of DNA degradation with the decrease in mitochondrial PBR ligand binding (r = 0.89). The GnRH-Ag-induced decrease in the 18-kDa PBR protein also correlated with the reduction in the Bcl-X(L), but not Bcl-2 (cell survival), gene product levels and the increase in the Bax (cell death) gene product expression in the luteal mitochondrial preparations. Considering the function of PBR in cholesterol uptake and intramitochondrial movement, we propose that decreased PBR expression may lead to reduced levels of mitochondrial membrane cholesterol, which, together with the ability of Bcl-X(L) and Bax to form ion channels, produces breaks in the outer membranes allowing the exit of cytochrome c, thus triggering apoptosis. Alternatively, PBR may exert an as yet unidentified anti-apoptotic function.
Papadopoulos
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Department of Cell Biology, Georgetown University Medical Center, Washington, DC 20007-2197, USA. papadopv@gunet.georgetown.edu
Dharmarajan
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AM
Li
H
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Culty
M
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Lemay
M
M
Sridaran
R
R
D000818:Animals; D017209:Apoptosis; D003338:Corpus Luteum / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists* / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000096:biosynthesis*; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
C494828:Bax protein, rat; C494813:Bcl2l1 protein, rat; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011963:Receptors, GABA-A; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D007987:Gonadotropin-Releasing Hormone; C030741:lutrelin acetate