title: Peripheral-type benzodiazepine receptors are involved in the regulation of cholesterol side chain cleavage in adrenocortical mitochondria.
abstract: In an attempt to elucidate the physiological relevance of the peripheral type of benzodiazepine receptor in adrenocortical mitochondria, we examined the effect of three different benzodiazepines (diazepam, Ro5-4864, and chlordiazepoxide) on the conversion of cholesterol to pregnenolone, the rate-limiting step in steroidogenesis, by using cholesterol-loaded mitochondria from bovine adrenal zona fasciculata. These benzodiazepines, except chlordiazepoxide, caused a dose-dependent stimulation of the cholesterol side chain cleavage in the mitochondria. The stimulatory effect of Ro5-4864 was approximately 10 times more potent than that of diazepam. No inhibitory effect of YM-684 (Ro15-1788), a potent antagonist to central-type benzodiazepine receptors, was observed in the stimulation induced by diazepam and Ro5-4864. Both external calcium ion and voltage-dependent calcium channel blocker, (+)-PN200-110, were without effect on the diazepam-induced steroidogenesis. By contrast, pretreatment of mitochondria with digitonin abolished the stimulatory effect of diazepam on the mitochondrial steroidogenesis. The present results indicate that the peripheral-type benzodiazepine receptor of adrenocortical mitochondria plays an essential role in regulating cholesterol side chain cleavage without any change of calcium channels.
authors.affiliation: Department of Pharmacology I, Jikei University School of Medicine, Tokyo.
authors.forename: K
authors.initials: K
authors.lastname: Yanagibashi
authors.forename: Y
authors.initials: Y
authors.lastname: Ohno
authors.forename: N
authors.initials: N
authors.lastname: Nakamichi
authors.forename: T
authors.initials: T
authors.lastname: Matsui
authors.forename: K
authors.initials: K
authors.lastname: Hayashida
authors.forename: M
authors.initials: M
authors.lastname: Takamura
authors.forename: K
authors.initials: K
authors.lastname: Yamada
authors.forename: S
authors.initials: S
authors.lastname: Tou
authors.forename: M
authors.initials: M
authors.lastname: Kawamura
mesh_terms: D000302:Adrenal Cortex / Q000648:ultrastructure*; D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002417:Cattle; D002784:Cholesterol / Q000378:metabolism*; D003975:Diazepam / Q000494:pharmacology; D004072:Digitonin / Q000494:pharmacology; D008928:Mitochondria / Q000378:metabolism*; D011284:Pregnenolone / Q000096:biosynthesis; D011963:Receptors, GABA-A / Q000378:metabolism*; D013256:Steroids / Q000096:biosynthesis
chemical_list: D011963:Receptors, GABA-A; D013256:Steroids; D001569:Benzodiazepines; D011284:Pregnenolone; D002784:Cholesterol; D004072:Digitonin; D003975:Diazepam; D002118:Calcium