Peripheral benzodiazepine receptor in cholesterol transport and steroidogenesis

@article{Papadopoulos1997PeripheralBR,
  title={Peripheral benzodiazepine receptor in cholesterol transport and steroidogenesis},
  author={Vassilios Papadopoulos and Hakima Amri and Noureddine Boujrad and Caterina Cascio and Martine Culty and Martine J Garnier and Matthew J Hardwick and H. Li and Branislav Vidi{\'c} and A. Shane Brown and J. L. Reversa and Jean Marie Bernassau and Katy Drieu},
  journal={Steroids},
  year={1997},
  volume={62},
  pages={21-28}
}
Steroidogenesis begins with the metabolism of cholesterol to pregnenolone by the inner mitochondrial membrane cytochrome P450 side-chain cleavage (P450scc) enzyme. The rate of steroid formation, however, depends on the rate of cholesterol transport from intracellular stores to the inner mitochondrial membrane and loading of P450scc with cholesterol. In previous in vitro studies, we demonstrated that a key element in the regulation of cholesterol transport is the mitochondrial peripheral-type… Expand
Peripheral-type benzodiazepine receptor: structure and function of a cholesterol-binding protein in steroid and bile acid biosynthesis
TLDR
The various polymeric states of PBR might be part of a cycle mediating cholesterol uptake and release into the mitochondria, with PBR functioning as a cholesterol exchanger against steroid product(s) arising from cytochrome P450 action. Expand
Molecular control of luteal secretion of progesterone.
TLDR
Fluorescence energy transfer procedures indicate that StAR associates with PBR in mitochondrial membranes, and 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. Expand
Cholesterol transport, peripheral benzodiazepine receptor, and steroidogenesis in aging Leydig cells.
TLDR
Results suggest that alterations in cholesterol transport and in PBR may play critical roles in age-related decreases in testosterone production in Brown Norway rat Leydig cells. Expand
CHAPTER 6 – Intracellular Cholesterol Dynamics in Steroidogenic Cells
TLDR
Observations not only indicated that it was the availability of cholesterol that limited pregnenolone production in earlier studies but also highlighted the importance of cellular cholesterol trafficking to steroidogenesis. Expand
Cholesterol transport in steroid biosynthesis: role of protein-protein interactions and implications in disease states.
TLDR
The focus of this review is on the intracellular pathways and protein-protein interactions involved in cholesterol transport and steroid biosynthesis and the roles and interactions of these proteins in endocrine pathologies and neurological diseases where steroid synthesis plays a critical role. Expand
Translocator protein-mediated pharmacology of cholesterol transport and steroidogenesis
TLDR
TSPO drug ligands have been proposed as therapeutic agents to regulate steroid levels in the brain and testis and are associated with depression, metabolic syndrome and reduced sexual function. Expand
Does cholesterol use the mitochondrial contact site as a conduit to the steroidogenic pathway?
  • M. Thomson
  • Biology, Medicine
  • BioEssays : news and reviews in molecular, cellular and developmental biology
  • 2003
The first and rate‐limiting step of steroidogenesis is the transfer of cholesterol from the outer mitochondrial membrane to the inner membrane where it is converted to pregnenolone by cytochrome P450Expand
Role of the peripheral-type benzodiazepine receptor in adrenal and brain steroidogenesis.
TLDR
The identification and characterization of the PBR, the evidence pointing to its function as a cholesterol pore involved in transporting cholesterol from the cytoplasm of steroid-producing cells into the inner mitochondrial membrane where it is metabolized, and the known mechanisms regulating its function are reviewed. Expand
The role of PBR/TSPO in steroid biosynthesis challenged.
TLDR
The events that regulate the rapid synthesis of steroid hormones in response to trophic hormone stimulation of the steroidogenic cells have been the ongoing subject of intense interest for several decades, and a list of the characteristics that the putative protein regulator appeared to possess have been described. Expand
Translocator protein (18 kDa): an update on its function in steroidogenesis
TLDR
Taken together, these studies suggest that TSPO is a unique mitochondrial pharmacological target for diseases that involve increased mitochondrial activity, including steroidogenesis. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 60 REFERENCES
Role of the peripheral-type benzodiazepine receptor and the polypeptide diazepam binding inhibitor in steroidogenesis
TLDR
A model where the interaction of DBI with PBR, at the outer/inner membrane contact sites, is the signal transducer of hormone-stimulated and constitutive steroidogenesis at the mitochondrial level is proposed. Expand
Regulation of cholesterol movement to mitochondrial cytochrome P450scc in steroid hormone synthesis
TLDR
It is suggested that hormonal activation, through these factors, alters membrane structure around mitochondrial intermembrane contact sites, which also function to transfer ADP, phospholipids, and proteins to the inner mitochondria. Expand
Mediation of the Hormonal Stimulation of Steroidogenesis by the Polypeptide Diazepam Binding Inhibitor
TLDR
The mechanisms by which pituitary trophic hormones act on their respective target organs, adrenal and gonads, to stimulate steroidogenesis have been under extensive investigation during the last 40 years. Expand
Peripheral-type benzodiazepine receptors are involved in the regulation of cholesterol side chain cleavage in adrenocortical mitochondria.
TLDR
The present results indicate that the peripheral-type benzodiazepine receptor of adrenocortical mitochondria plays an essential role in regulating cholesterol side chain cleavage without any change of calcium channels. Expand
Peripheral-type benzodiazepine receptors mediate translocation of cholesterol from outer to inner mitochondrial membranes in adrenocortical cells.
TLDR
The current study elucidates the specific step in the steroid biosynthetic pathway by which PBR mediate the stimulation in steroid hormone production and suggests that mitochondrial intermembrane cholesterol transport in steroidogenic cells is mediated by a mechanism coupled to PBR. Expand
Hormone-stimulated steroidogenesis is coupled to mitochondrial benzodiazepine receptors. Tropic hormone action on steroid biosynthesis is inhibited by flunitrazepam.
TLDR
Observations provide unequivocal evidence that the antagonistic action of flunitrazepam is mediated through its interaction with MBR demonstrating that these drug recognition sites are coupled to steroid biosynthesis activated by tropic hormones. Expand
Pregnenolone biosynthesis in C6-2B glioma cell mitochondria: regulation by a mitochondrial diazepam binding inhibitor receptor.
TLDR
The present work shows that mitochondria of C6-2B cells convert (22R)-22-hydroxycholesterol to pregnenolone by a mechanism blocked by aminoglutethimide, and proposes to term this mitochondrial receptor MDR (mitochondrial DBI receptor) to indicate its responsiveness to DBI in steroid biosynthesis. Expand
Trophic stimulation of steroidogenesis: in search of the elusive trigger.
  • P. Hall
  • Biology, Medicine
  • Recent progress in hormone research
  • 1985
TLDR
Purification of the side-chain cleavage enzyme from beef adrenal reveals important properties of the enzyme, such as the stoichiometry of the reaction, the involvement of heme in the cleavage of 20,22 bond, and aggregation of the enzymes to an active form composed of 16 subunits, however the mechanism of action of ACTH is still unknown. Expand
Diazepam binding inhibitor and its processing products stimulate mitochondrial steroid biosynthesis via an interaction with mitochondrial benzodiazepine receptors.
TLDR
Flunitrazepam, a benzodiazepine that binds with high nanomolar affinity to MBR, was recently shown to act as an antagonist of ACTH and LH/hCG-induced steroidogenesis and was found in the present studies to inhibit DBI-stimulated mitochondrial steroidogenesis. Expand
Acute action of choriogonadotropin on Leydig tumor cells: induction of a higher affinity benzodiazepine-binding site related to steroid biosynthesis.
TLDR
In MA-10 cells, the most rapid effect described thus far of hCG and cAMP, is the transient induction of a higher affinity benzodiazepine-binding site, which occurs concomitantly with an increase in the rate of steroid formation. Expand
...
1
2
3
4
5
...