Diazepam-binding inhibitor (DBI)-processing products, acting at the mitochondrial DBI receptor, mediate adrenocorticotropic hormone-induced steroidogenesis in rat adrenal gland.
- 15 November 1992
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 89 (22), 10598-10602
- https://doi.org/10.1073/pnas.89.22.10598
Abstract
Diazepam-binding inhibitor (DBI) is a 9-kDa polypeptide that colocalizes in glial, adrenocortical, and Leydig cells with the mitochondrial DBI receptor (MDR). By binding with high affinity to the MDR, DBI and one of its processing products--DBI-(17-50)--regulate pregnenolone synthesis and have been suggested to participate in the immediate activation of adrenal steroidogenesis by adrenocorticotropic hormone (ACTH). In adrenals of hypophysectomized rats (1 day after surgery), ACTH failed to acutely affect the amount of adrenal DBI and the density of MDR but increased the rate of DBI processing, as determined by the HPLC profile of DBI-(17-50)-like immunoreactivity. The similar latency times for this effect and for ACTH stimulation of adrenal steroidogenesis suggest that the two processes are related. The ACTH-induced increase in both adrenal steroidogenesis and rate of DBI processing were completely inhibited by cycloheximide; this result suggests the requirement for the de novo synthesis of a protein with a short half-life, probably an endopeptidase. This enzyme, under the influence of ACTH, may activate formation of a DBI-processing product that stimulates steroidogenesis via the MDR. In support of this hypothesis is the demonstration that in hypophysectomized rats the MDR antagonist PK 11195 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxam ide completely inhibited the adrenal steroidogenesis stimulated by ACTH and by the high-affinity MDR ligand 4'-chlorodiazepam.Keywords
This publication has 38 references indexed in Scilit:
- Diazepam binding inhibitor processing in the rhesus monkey brain: An immunocytochemical studyJournal of Chemical Neuroanatomy, 1992
- Endozepine/diazepam binding inhibitor in adrenocortical and Leydig cell lines: Absence of hormonal regulationMolecular and Cellular Endocrinology, 1992
- The role of diazepam binding inhibitor and its processing products at mitochondrial benzodiazepine receptors: Regulation of steroid biosynthesisNeuropharmacology, 1991
- Diazepam binding inhibitor (DBI): A peptide with multiple biological actionsLife Sciences, 1991
- Isolation and Characterization of a Rat Brain Triakontatetraneuropeptide, a Posttranslational Product of Diazepam Binding Inhibitor: Specific Action at the Ro 5‐4864 Recognition SiteJournal of Neurochemistry, 1989
- Regulation of the Synthesis of Steroidogenic Enzymes in Adrenal Cortical Cells by ACTHAnnual Review of Physiology, 1988
- Subcellular Location and Neuronal Release of Diazepam Binding InhibitorJournal of Neurochemistry, 1987
- ACTH regulation of cholesterol movement in isolated adrenal cellsJournal of Steroid Biochemistry, 1987
- Opposite effects of two ligands for peripheral type benzodiazepine binding sites, PK 11195 and RO5-4864, in a conflict situation in the ratLife Sciences, 1985
- Isolation of biologically active ribonucleic acid from sources enriched in ribonucleaseBiochemistry, 1979