Calmidazolium and other imidazole compounds affect steroidogenesis in Y1 cells: lack of involvement of the peripheral-type benzodiazepine receptor.
Calmidazolium potently stimulated steroidogenesis in a mouse adrenocortical Y1 cell line, in a Ca(2+)-independent manner, an effect similar to that reported by Choi and Cooke [1] for rat primary adrenocortical and Leydig cells. Calmidazolium analogues, econazole and miconazole, were shown to inhibit both this calmidazolium-stimulated rate and the endogenous rate of steroidogenesis. In determining the mechanism by which imidazole compounds affect steroidogenesis, they were found not to act directly on the mitochondrial Cyt P-450scc enzyme, making it likely that they act instead on the intramitochondrial transport of cholesterol. Using competition binding studies, calmidazolium, econazole and miconazole were subsequently identified as novel ligands for the peripheral-type benzodiazepine receptor (PBR). Econazole and miconazole were found to inhibit stimulation by PK 11195 (a specific PBR ligand) of steroidogenesis, whereas treatment of the cells with calmidazolium and PK 11195 at the same time resulted in an additive stimulatory effect on steroidogenesis. These results suggest that the effects of these substituted imidazoles on steroidogenesis in Y1 cells is not mediated through their interaction with the PBR.
Zisterer
D M
DM
Department of Biochemistry, Trinity College, Dublin, Ireland.
Williams
D C
DC
D000302:Adrenal Cortex / Q000187:drug effects*; D000818:Animals; D001667:Binding, Competitive; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004464:Econazole / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D008024:Ligands; D051379:Mice; D008825:Miconazole / Q000494:pharmacology; D011284:Pregnenolone / Q000096:biosynthesis*; D011963:Receptors, GABA-A / Q000378:metabolism*
D007093:Imidazoles; D007546:Isoquinolines; D008024:Ligands; D011963:Receptors, GABA-A; C031938:calmidazolium; D004464:Econazole; D011284:Pregnenolone; D008825:Miconazole; D002786:Cholesterol Side-Chain Cleavage Enzyme; C037850:PK 11195