Developmental expression of the peripheral-type benzodiazepine receptor and the advent of steroidogenesis in rat adrenal glands

Although the precise mechanism whereby cholesterol is transported across th e outer mitochondrial membrane is uncertain, a multimeric receptor complex termed the peripheral-type benzodiazepine receptor (PBR) appears essential for this process. We therefore predicted that adrenal cells at different de velopmental stages would express PER coincidentally with the advent of ster oidogenesis. Adrenals of neonatal rats demonstrate greatly reduced sensitiv ity to ACTH that gradually increases after the first 2 weeks of life. Thus, neonates have lower circulating corticosterone levels following exposure t o stress. We examined mitochondrial PER ligand binding activity, immunoreac tive (ir) PER content, and adrenal sensitivity to ACTH in vivo and in vitro . Ontogeny of both mitochondrial PER ligand binding capacity and irPBR dire ctly paralleled that of ACTH-inducible steroidogenesis in isolated rat adre nal cells and in rats injected with ACTH. In addition, neonatal PER had app roximately 2-fold higher affinity for PK11195, a synthetic ligand that bind s with high affinity to PER. No correlation was observed during neonatal li fe between ir-steroidogenic acute regulatory (StAR) protein content and ste roidogenesis. These results are consistent with the hypothesis that PER is an absolute prerequisite for adrenocortical steroidogenesis, and suggest th at the stress hyporesponsive period of neonatal rats may result from decrea sed PER expression. In addition, the higher affinity of neonatal PER and th e relatively high basal expression of StAR protein in neonatal adrenals may partly explain the high constitutive steroidogenesis characteristic of neo natal rat adrenal cells.