NCBI Summary:
Present mainly in the mitochondrial compartment of peripheral tissues, the protein encoded by this gene interacts with some benzodiazepines and has different affinities than its endogenous counterpart. The protein is a key factor in the flow of cholesterol into mitochondria to permit the initiation of steroid hormone synthesis. Alternatively spliced transcript variants have been reported; one of the variants lacks an internal exon and is considered non-coding, and the other variants encode the same protein. [provided by RefSeq, Feb 2012]
General function
Receptor
Comment
Cellular localization
Mitochondrial
Comment
Ovarian function
Ovulation, Steroid metabolism, Luteinization
Comment
Disorders of folliculogenesis are associated with abnormal expression of peripheral benzodiazepine receptors in granulosa cells. Pozhilenkova EA et al. We studied apoptosis and expression of peripheral benzodiazepine receptors in granulosa cells of dominant follicles from women with endocrine sterility. The expression of peripheral benzodiazepine receptors in granulosa cells depends on the degree of granulosa cell apoptosis and type of disorders in follicular steroidogenesis, which suggests the involvement of peripheral benzodiazepine receptors into the regulation of folliculogenesis in health and disease.
Expression regulated by
LH, Eicosanoids
Comment
Gene expression profiling of bovine preovulatory follicles: Gonadotropin surge and prostanoid dependent up-regulation of genes potentially linked to the ovulatory process. Li Q et al. The molecular mechanisms of ovulation and luteinization have not been well established, partially due to lack of a comprehensive understanding of functionally significant genes up-regulated in response to an ovulatory stimulus and the signaling pathways involved. In the present study, transcripts increased in bovine preovulatory follicles following a GnRH-induced LH surge were identified using microarray technology. Increased expression of 368 and 878 genes was detected at 12 (368 genes) and 20 h (878 genes) following GnRH injection. The temporal, cell specific and prostanoid dependent regulation of selected genes (ADAM10, DBI, CD36, MTSS1, TFG, and RABGAP1) identified from microarray studies and related genes (ADAM17, AREG) of potential significance were also investigated. Expression of mRNA for DBI and CD36 was simultaneously up-regulated in theca and granulosa cells following the LH surge, whereas temporal regulation of ADAM10, MTSS1, TFG and RABGAP1 was distinct in the two cell compartments and increased granulosa TFG and RABGAP1 mRNA was prostanoid dependent. AREG mRNA was increased in theca and granulosa cells at 12 and 24 h following GnRH injection. ADAM17 mRNA was increased in theca, but reduced in granulosa cells 24 h following GnRH injection. The increased ADAM17 and AREG mRNA was prostanoid dependent. ADAM10 and ADAM17 protein were increased specifically in the apex but not the base of preovulatory follicles and the increase in ADAM17 was prostanoid dependent. Results reveal novel information on regulation of preovulatory gene expression and suggest a potential functional role for ADAM10 and ADAM17 proteins in the region of follicle rupture.
Exhaustive analysis of the location of the peripheral benzodiazepine receptor (PBR) both at the subcellular and the tissue level is warranted to gain a better understanding of its biological roles. To date, many studies have been performed in animal models, such as rat, mouse, and pig, that yielded important information. However, only a few reports were dedicated to the analysis of PBR expression in humans. To enlarge on previous studies, Bribes E, et al investigated PBR expression in different human organs using the monoclonal antibody 8D7 that specifically recognized the human PBR. In the ovary (Figure 6A), which was of postmenopausal status with an atretic corpus albicans, sparse cells of the cortex demonstrated strong granular cytoplasmic staining. The remaining secretory cells in a degenerating corpus albicans were moderately stained. The columnar cells of the surface epithelium were strongly positive for 8D7 immunostaining.
The Role of Ets Transcription Factors in the Basal Transcription of the Translocator Protein (18 kDa). Giatzakis C et al. The translocator protein (18 kDa; TSPO), previously known as peripheral-type benzodiazepine receptor, is a high-affinity cholesterol- and drug-binding mitochondrial protein involved in various cell functions including steroidogenesis, apoptosis, and proliferation. TSPO is highly expressed in secretory and glandular tissues, especially in steroidogenic cells, and its expression is altered in certain pathological conditions such as cancer and neurological diseases. In this study, we characterized the regulatory elements present in the region of the TPSO promoter extending from 515 to 805 bp upstream of the transcription start site, an area previously identified as being important for transcription. Promoter fragments extending 2.7 kb and 805 bp upstream of the transcription start site were able to direct enhanced green fluorescent protein expression to Leydig cells of the testis, theca cells of the ovary, and cells of the adrenal cortex in transgenic animals. This expression pattern perfectly mimicked endogenous TSPO expression. Functional characterization of the 515-805 bp region revealed the presence of one specificity protein 1/specificity protein 3 (Sp1/Sp3) and two v-ets erythroblastosis virus E26 oncogene homologue (Ets) binding sites that are important for transcriptional activity in both MA-10 mouse Leydig tumor cells and NIH/3T3 whole mouse embryo fibroblasts. GA-binding protein alpha (GABPalpha), a member of the Ets family of transcription factors, was found to be associated with the endogenous TSPO promoter. We conclude that Sp1/Sp3 and members of the Ets family of transcription factors bind to specific binding sites in the TSPO promoter to drive basal TSPO gene transcription.
Follicle stages
Corpus luteum
Comment
Molecular control of luteal secretion of progesteroneNiswender GD..
Cholesterol provided by low- or high-density lipoprotein is the precursor for biosynthesis of progesterone. Once inside the cell, cholesterol can be used for steroidogenesis or esterified with long-chain fatty acids and stored as cholesterol esters in lipid droplets. When it is needed for steroidogenesis, free cholesterol is transported to the mitochondrion via a mechanism that involves cytoskeletal elements and sterol carrier proteins. Cytochrome P450 cholesterol side chain cleavage enzyme complex converts the cholesterol to pregnenolone, which is then converted to progesterone by 3beta-hydroxysteroid dehydrogenase/delta5,delta4 isomerase in the smooth endoplasmic reticulum. Transport of cholesterol from the cytoplasm to the inner mitochondrial membrane is both the rate-limiting step in progesterone biosynthesis and the step most acutely influenced by second messengers. Steroidogenic acute regulatory protein (StAR) and peripheral-type benzodiazepine receptors (PBR) are involved in this transport. StAR may bind cholesterol in the cytosol and transport it to the mitochondrial membrane where PBR is involved in transport from the outer to the inner mitochondrial membrane. Phosphorylation of StAR by protein kinase A (PKA) stimulates cholesterol transport, whereas phosphorylation by PKC may inhibit this process. Endozepine, the natural ligand for PBR, also appears to be involved in regulation of the rate of cholesterol transport to the inner mitochondrial membrane and to play a role in the stimulatory effects of PKA on steroidogenesis. Increased concentrations of endozepine were detected in large luteal cells, and may explain the increased progesterone secretion from this type of cell. Fluorescence energy transfer procedures indicate that StAR associates with PBR in mitochondrial membranes. A model is presented for the proposed interactions of StAR, PBR and endozepine in the transport of cholesterol from the outer to the inner mitochondrial membrane.