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-relea sing hormone agonist (GnRH-Ag) decreases the expression of the mitochondria l peripheral-type benzodiazepine receptor (PBR) and increases the rate of D NA 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 fragmen tation and correlate the increase of the rate of DNA degradation with the d ecrease in mitochondrial PER ligand binding (r = 0.89). The GnRH-Ag-induced decrease in the 18-kDa PER protein also correlated with the reduction in t he Bcl-X-L, but not Bcl-2 (cell survival), gene product levels and the incr ease in the Bar (cell death) gene product expression in the luteal mitochon drial preparations. Considering the function of PER in cholesterol uptake a nd intramitochondrial movement, we propose that decreased PER expression ma y lead to reduced levels of mitochondrial membrane cholesterol, which, toge ther with the ability of Bcl-X-L and Bar to form ion channels, produces bre aks in the outer membranes allowing the exit of cytochrome c, thus triggeri ng apoptosis. Alternatively, PER may exert an as yet unidentified anti-apop totic function. (C) 1999 Elsevier Science Inc.