CALMIDAZOLIUM AND OTHER IMIDAZOLE COMPOUNDS AFFECT STEROIDOGENESIS INY1 CELLS - LACK OF INVOLVEMENT OF THE PERIPHERAL-TYPE BENZODIAZEPINE RECEPTOR

Calmidazolium potently stimulated steroidogenesis in a mouse adrenocor tical Y1 cell line, in a Ca2+-independent manner, an effect similar to that reported by Choi and Cooke [1] for rat primary adrenocortical an d Leydig cells. Calmidazolium analogues, econazole and miconazole, wer e shown to inhibit both this calmidazolium-stimulated rate and the end ogenous rate of steroidogenesis. In determining the mechanism by which imidazole compounds affect steroidogenesis, they were found not to ac t directly on the mitochondrial Cyt P-450scc enzyme, making it likely that they act instead on the intramitochondrial transport of cholester ol. Using competition binding studies, calmidazolium, econazole and mi conazole were subsequently identified as novel ligands for the periphe ral-type benzodiazepine receptor (PER). Econazole and miconazole were found to inhibit stimulation by PK 11195 (a specific PER ligand) of st eroidogenesis, whereas treatment of the cells with calmidazolium and P K 11195 at the same time resulted in an additive stimulatory effect on steroidogenesis. These results suggest that the effects of these subs tituted imidazoles on steroidogenesis in Y1 cells is not mediated thro ugh their interaction with the PBR. (C) 1997 Elsevier Science Ltd.