In vivo studies on the role of the peripheral benzodiazepine receptor (PBR) in steroidogenesis

In various steroidogenic cell models, mitochondrial preparations and submit ochondrial fractions, the expression of the mitochondrial 18 kDa peripheral -type benzodiazepine receptor (PBR) protein confers the ability to take up and release, upon ligand activation, cholesterol. Thus, cholesterol becomes available to P450scc on the inner mitochondrial membrane. These in vitro s tudies were validated by in vivo experiments. Treatment of rats with ginkgo lide B (GKB), specifically reduced the ligand binding capacity, protein, an d mRNA expression of the adrenocortical PER and circulating glucocorticoid levels. Treatment with GKB also resulted in inhibition of PER protein synth esis and corticosterone production by isolated adrenocortical cells in resp onse to ACTH. The ontogeny of both PER binding capacity and protein directl y paralleled that of ACTH-inducible steroidogenesis in rat adrenal cells an d in rats injected with ACTH. In addition, the previously described suppres sion of luteal progesterone synthesis in the pregnant rat by continuous in vivo administration of a gonadotropin-releasing hormone agonist may be due to decreased luteal PER ligand binding and mRNA. These results suggest that (i) PER is an absolute prerequisite for adrenocortical and luteal steroido genesis, (ii) regulation of adrenal PER expression may be used as a tool to control circulating glucocorticoid levels and (iii) the stress hypo-respon sive period of neonatal rats may result from decreased adrenal cortical PER expression.