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The peripheral-type benzodiazepine receptor is functionally linked to Leydig cell steroidogenesis
V Papadopoulos1, A G Mukhin, E Costa
1Department of Anatomy and Cell Biology, Georgetown University School of Medicine, Washington, D.C. 20007.
The Journal of Biological Chemistry
|March 5, 1990
Summary
Peripheral-type benzodiazepine receptors (PBR) are functionally linked to Leydig cell steroid biosynthesis. PBR ligands stimulate steroid production by regulating cholesterol availability within mitochondria.
Area of Science:
- Endocrinology
- Mitochondrial Biology
- Steroidogenesis
Background:
- Testicular mitochondria possess peripheral-type benzodiazepine receptors (PBR).
- Previous studies purified, cloned, and expressed an 18,000 Mr PBR protein.
Purpose of the Study:
- To investigate the functional link between PBR and Leydig cell steroid biosynthesis.
- To determine the role of PBR ligands in modulating steroidogenesis.
Main Methods:
- Tested nine different PBR ligands for their potency to modulate steroidogenesis in MA-10 mouse Leydig tumor cells.
- Assessed the effect of PBR ligands on pregnenolone biosynthesis in isolated mitochondria and mitoplasts.
- Measured cytochrome P-450 side chain cleavage activity in intact cells and purified rat Leydig cells.
Main Results:
- A strong correlation (r=0.95) was observed between PBR ligand binding affinity and steroid biosynthesis potency.
- PBR ligands stimulated steroid production up to 4-fold, independent of cycloheximide.
- PBR ligands stimulated pregnenolone biosynthesis in isolated mitochondria, suggesting a role in cholesterol transport.
Conclusions:
- Peripheral-type benzodiazepine receptors are implicated in the acute stimulation of Leydig cell steroidogenesis.
- PBR may mediate cholesterol entry, distribution, and/or availability within mitochondria.
- These findings highlight a novel regulatory pathway in steroid hormone production.