ROLE OF PERIPHERAL-TYPE BENZODIAZEPINE RECEPTORS IN STEROIDOGENESIS

Peripheral-type benzodiazepine (BZ) receptors (PBRs) have been identif ied in various peripheral tissues as well as in glial cells in the bra in. PBRs are located mainly on the outer mitochondrial membrane and bi nd with high affinity the BZ Ro 5-4864 (4'-cholorodiazepam) and the no n-BZ PK 11195 (an isoquinoline carboxamide derivative), but bind with very low affinity the BZ clonazepam. PBRs have been cloned from variou s species. PBRs are multimeric receptors composed of the 18-kDa bindin g site for isoquinolines, the 32-kDa voltage-dependent anion channel, and the 30-kDa adenine nucleotide carrier (which binds BZs). The expre ssion of PBRs is especially high in steroidogenic organs. Steroid admi nistration affects PBR density, whereas depletion of hormones by hypop hysectomy in female rats, or castration (surgical or chemical) in male rats, decreases PBR density in endocrine organs, which can be elevate d to normal values after administration of the appropriate hormone. PB Rs are probably involved in several functions, including cell prolifer ation, respiration, and steroidogenesis. It has been suggested that PB Rs are involved in the translocation of cholesterol from the outer to the inner membrane of the mitochondria and have an effect on the biosy nthesis of steroids.