Mitochondrial peripheral-type benzodiazepine receptor (PBR) is an indispensable element of the steroidogenic machinery, where it mediates the delivery of cholesterol to the inner mitochondrial side chain cleavage cytochrome P-450 upon ligand activation. PBR is composed of three subunits, an isoquinoline binding site, a voltage-dependent anion channel and an adenine nucleotide carrier. PBR is genetically conserved from bacteria to humans and in humans is widely expressed in peripheral organs, whereas in the brain, it is sparse and located mainly in glial cells. Peroxisome proliferator perfluordecanoic acid (PFDA) inhibits the Leydig cell steroidogenesis by affecting PBR mRNA stability, thus inhibiting PBR expression, cholesterol transport into the mitochondria and subsequent steroid formation. A cytoplasmic protein, PRAX-1 ( peripheral benzodiazepine receptor-associated protein 1), is found to specifically interact with PBR. The polypeptide diazepam binding inhibitor is an endogenous PBR ligand. PBR also binds Ro 5-4864 (4-chlorodiazepam) and PK 11185 (an isoquinoline carboxamide derivative), but not clonazepam, and PBR regulates the cholesterol transport that results in decreased circulating corticosterone levels.
