Mitochondrial benzodiazepine receptors regulate steroid biosynthesis

Journal Article · Fri Dec 01 04:00:00 EST 1989 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.86.24.9813· OSTI ID:6921570

Mukhin, A G; Papadopoulos, V; Costa, E; Krueger, K E ^[1]

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1. Georgetown Univ. School of Medicine, Washington, DC (USA)

Recent observations on the steroid synthetic capability within the brain open the possibility that benzodiazepines may influence steroid synthesis in nervous tissue through interactions with peripheral-type benzodiazepine recognition sites, which are highly expressed in steroidogenic cells and associated with the outer mitochondrial membrane. To examine this possibility nine molecules that exhibit a greater than 10,000-fold difference in their affinities for peripheral-type benzodiazepine binding sites were tested for their effects on a well-established steroidogenic model system, the Y-1 mouse adrenal tumor cell line. 4{prime}-Chlorodiazepam, PK 11195, and PK 14067 stimulated steroid production by 2-fold in Y-1 cells, whereas diazepam, flunitrazepam, zolpidem, and PK 14068 displayed a lower (1.2- to 1.5-fold) maximal stimulation. In contrast, clonazepam and flumazenil did not stimulate steroid synthesis. The potencies of these compounds to inhibit {sup 3}H-labeled PK 11195 binding to peripheral-type benzodiazepine recognition sites correlated with their potencies to stimulate steroid production. Similar findings were observed in bovine and rat adrenocortical cell preparations. These results suggest that ligands of the peripheral-type benzodiazepine recognition site acting on this mitochondrial receptor can enhance steroid production. This action may contribute specificity to the pharmacological profile of drugs preferentially acting on the benzodiazepine recognition site associated with the outer membrane of certain mitochondrial populations.

• OSTI ID: 6921570
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 86:24; ISSN PNASA; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
AMINOBUTYRIC ACID
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOCHEMICAL REACTION KINETICS
BIOSYNTHESIS
CARBOXYLIC ACIDS
CATTLE
CELL CONSTITUENTS
CHOLESTEROL
COUNTING TECHNIQUES
DOMESTIC ANIMALS
DRUGS
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
MAMMALS
MEMBRANE PROTEINS
MITOCHONDRIA
NEUROREGULATORS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANOIDS
PHARMACOLOGY
PROTEINS
RADIORECEPTOR ASSAY
RATS
REACTION KINETICS
RECEPTORS
RODENTS
RUMINANTS
SCINTILLATION COUNTING
STEROIDS
STEROLS
SYNTHESIS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES