Benzodiazepines modulate signal transduction at type A GABA (gamma-aminobutyric acid) receptors (137160) located in brain synapses. GABA is the predominant inhibitory neurotransmitter of the mammalian central nervous system. This receptor binds GABA, beta-carbolines, and benzodiazepines with high affinity and a chloride ion channel. Benzodiazepines prolong the chloride ion channel opening burst elicited by GABA and thereby enhance GABA-mediated inhibitory responses. This facilitation plays a role in reducing pathologic anxiety. An endogenous ligand has been identified that is recognized by the beta-carboline/benzodiazepine recognition site located in the GABA receptor. This ligand, diazepam binding inhibitor (DBI), is a protein of about 11 kD that displaces beta-carbolines and benzodiazepines bound to brain membrane fractions in vitro. DBI or a derivative small neuropeptide is thought to downregulate the effects of GABA. Gray et al. (1986) isolated a cDNA clone that encodes human DBI. A polypeptide related to DBI, with similar binding activity to diazepam, has been isolated from human and bovine brain. This protein, called endozepine, contains 86 amino residues.
NCBI Summary:
This gene encodes diazepam binding inhibitor, a protein that is regulated by hormones and is involved in lipid metabolism and the displacement of beta-carbolines and benzodiazepines, which modulate signal transduction at type A gamma-aminobutyric acid receptors located in brain synapses. The protein is conserved from yeast to mammals, with the most highly conserved domain consisting of seven contiguous residues that constitute the hydrophobic binding site for medium- and long-chain acyl-Coenzyme A esters. Diazepam binding inhibitor is also known to mediate the feedback regulation of pancreatic secretion and the postprandial release of cholecystokinin, in addition to its role as a mediator in corticotropin-dependent adrenal steroidogenesis. Three pseudogenes located on chromosomes 6, 8 and 16 have been identified. Multiple transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]
General function
Ligand
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Cellular localization
Secreted, Cytoplasmic
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Ovarian function
Steroid metabolism, Luteinization, Oogenesis
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Bovine ovarian follicular growth and development correlate with lysophosphatidic acid expression. Sinderewicz E et al. (2017) The basis of successful reproduction is proper ovarian follicular growth and development. In addition to prostaglandins and vascular endothelial growth factor, a number of novel factors are suggested as important regulators of follicular growth and development: PGES, TFG, CD36, RABGAP1, DBI and BTC. This study focuses on examining the expression of these factors in granulosa and thecal cells that originate from different ovarian follicle types and their link with the expression of lysophosphatidic acid (LPA), known local regulator of reproductive functions in the cow. Ovarian follicles were divided into healthy, transitional, and atretic categories. The mRNA expression levels for PGES, TFG, CD36, RABGAP1, DBI and BTC in granulosa and thecal cells in different follicle types were measured by real-time PCR. The correlations among expression of enzymes synthesizing LPA (autotaxin, phospholipase A2), receptors for LPA and examined factors were measured. Immunolocalization of PGES, TFG, CD36, RABGAP1, DBI and BTC was examined by immunohistochemistry. We investigated follicle-type dependent mRNA expression of factors potentially involved in ovarian follicular growth and development, both in granulosa and thecal cells of bovine ovarian follicles. Strong correlations among receptors for LPA, enzymes synthesizing LPA, and the examined factors in healthy and transitional follicles were observed, with its strongest interconnection with TFG, DBI and RABGAP1 in granulosa cells, and TFG in thecal cells; whereas no correlations in atretic follicles were detected. A greater number of correlations were found in thecal cells than in granulosa cells as well as in healthy follicles than in transitional follicles. These data indicate the role of LPA in the growth, development and physiology of the bovine ovarian follicle.//////////////////
Expression regulated by
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Ovarian localization
Luteal cells
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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.