The human peripheral renzodiazepine receptor gene: Cloning and characterization of alternative splicing in normal tissues and in a patient with congenital lipoid adrenal hyperplasia
Abstract
The mitochondrial benzodiazepine receptor (mBzR) appears to be a key factor in the flow of cholesterol into mitochondria to permit the initiation of steroid hormone synthesis. The mBzR consists of three components; the 18-kDa component on the outer mitochondrial membrane appears to contain the benzodiazepine binding site, and is hence often termed the peripheral benzodiazepine receptor (PBR). Using a cloned human PBR cDNA as probe, we have cloned the human PBR gene. The 13-kb gene is divided into four exons, with exon 1 encoding only a short 5' untranslated segment. The 5' flanking DNA lacks TATA and CAAT boxes but contains a cluster of SP-1 binding sites, typical of "house-keeping" genes. The encoded PBR mRNA is alternately spliced into two forms: "authentic" PBR mRNA retains all four exons, while a short form termed PBR-S lacks exon 2. While PBR-S contains a 102-codon open reading frame with a typical initiator sequence, the reading frame differs from that of PBR, so that the encoded protein is unrelated to PBR. RT-PCR and RNase protection experiments confirm that both PBR and PBR-S are expressed in all tissues examined and that expression PBR-S is about 10 times the level of PBR. Expression of PBR cDNA in pCMV5 vectors transfected into COS-1 cells resulted in increased binding of [3H]PK11195, but expression of PBR-S did not. It has been speculated that patients with congenital lipoid adrenal hyperplasia, who cannot make any steroids, might have a genetic lesion in mBzR. RT…
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Different human (and other mammalian) isoforms of TSPO exist.
“studies have shown that different human (and other mammalian) isoforms of TSPO exist [56–58].”
From Expression of the translocator protein of 18 kDa by microglia, macrophages and astrocytes based on immunohistochemical localization in abnormal human brain (2009) · cites this paper as [57]
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Self-citationMissense mutation serine106—-proline causes 17 alpha-hydroxylase deficiency
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Self-citationCloning and sequence of the human adrenodoxin reductase gene
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Role of steroidogenic acute regulatory protein in adrenal and gonadal steroidogenesis
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Self-citationThe pathophysiology and genetics of congenital lipoid adrenal hyperplasia
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Self-citationEnigma of the peripheral benzodiazepine receptor
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Disorders in the initial steps of steroid hormone synthesis
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- Authors
- Lin, D., Chang, Y. J., Strauss, J. F., & Miller, W. L.
- Affiliations
- University of California, San Francisco (US)
- University of Pennsylvania (US)
- Corresponding author
- Miller, Walter L.
- Venue
- Genomics
- Publisher
- Elsevier BV
- Published
- 1993-12
- Volume
- 18
- Issue
- 3
- Pages
- 643-650
- ISSN
- 0888-7543 (ISSN-L)
- OpenAlex
- W2038247021
- Cited by
- 86
- References
- 5
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 2 · 2020: 1 · 2017: 1 · 2016: 3 · 2015: 2 · 2014: 3 · 2013: 2 · 2012: 2
- FWCI
- 5.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Genomics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01dk042154-09, 5p30hd028825-10)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-37922, DK 42154, R01DK037922)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD-28825)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- translocator protein (TSPO), alternative splicing, gene cloning, 5'-flanking region, Sp1 binding site, congenital lipoid adrenal hyperplasia, steroidogenesis, cholesterol transport, testicular gene expression
- MeSH terms
- Adrenal Hyperplasia, Congenital, Amino Acid Sequence, Animals, Base Sequence, Brain, Cell Line, Cloning, Molecular, Exons, Female, Fetus, Humans, Intracellular Membranes, Isoquinolines, Leydig Cell Tumor, Male, Mitochondria, Molecular Sequence Data, Organ Specificity, Placenta, Pregnancy, Promoter Regions, Genetic, Receptors, GABA-A, Recombinant Proteins, Reference Values, RNA, Messenger, Testicular Neoplasms, Testis, Transcription, Genetic, Transfection, Hominidae, Polymerase Chain Reaction, TATA Box, Alternative Splicing
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