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Mitochondrial benzodiazepine receptors regulate steroid biosynthesis
A G Mukhin1, V Papadopoulos, E Costa
1Fidia-Georgetown Institute for the Neurosciences, Georgetown University School of Medicine, Washington, DC 20007.
Summary
Benzodiazepines can influence brain steroid synthesis by interacting with specific mitochondrial sites. This study shows that ligands targeting these peripheral-type benzodiazepine sites enhance steroid production in adrenal cells.
Area of Science:
- Neuroendocrinology
- Mitochondrial Biology
- Pharmacology
Background:
- The brain possesses steroid synthetic capabilities, suggesting potential interactions with neuroactive compounds.
- Peripheral-type benzodiazepine recognition sites are located on the outer mitochondrial membrane and are abundant in steroidogenic cells.
Purpose of the Study:
- To investigate whether benzodiazepines influence steroid synthesis via peripheral-type benzodiazepine recognition sites.
- To determine the correlation between ligand affinity for these sites and steroidogenic activity.
Main Methods:
- Testing nine molecules with varying affinities for peripheral-type benzodiazepine binding sites.
- Utilizing the Y-1 mouse adrenal tumor cell line as a steroidogenic model system.
- Assessing steroid production and binding affinities in bovine and rat adrenocortical cells.
Main Results:
- Certain benzodiazepine derivatives (4'-Chlorodiazepam, PK 11195, PK 14067) significantly stimulated steroid production (2-fold).
- A strong correlation (r = 0.985) was observed between the potency of ligands to inhibit binding to peripheral-type benzodiazepine sites and their ability to stimulate steroid production.
- Similar effects were confirmed in bovine and rat adrenocortical cells.
Conclusions:
- Ligands acting on mitochondrial peripheral-type benzodiazepine recognition sites can enhance steroid production.
- This interaction may contribute to the specific pharmacological actions of drugs targeting these mitochondrial sites.