Reversible Changes in Adrenocorticotropin (ACTH)-Induced Adrenocortical Steroidogenesis and Expression of the Peripheral-Type Benzodiazepine Receptor during the ACTH-Insensitive Period in Young Rats

Abstract

We previously demonstrated decreased adrenal content of a mitochondrial cholesterol transporter [peripheral-type benzodiazepine receptor (PBR)] during the first postnatal week in rats, when ACTH-inducible steroidogenesis is low. Here we report that the expression of PBR protein and mRNA increases throughout the neonatal/juvenile period in rats in parallel with ACTH-inducible steroidogenesis in vitro. We also previously reported that chronic stimulation of rat pups with daily ACTH injections augmented the steroidogenic response of the developing adrenal cortex. We therefore tested the hypotheses that the change in phenotype induced by ACTH was permanent, and that the effects of ACTH were mediated by increased PBR expression. Pups were injected with ACTH or saline from postnatal d (pd) 2-8 or 2-14. Another group of pups received ACTH from pd 2-7, followed by saline from pd 8-14. On the final day, all pups were challenged with a test injection of ACTH or saline. Exposure to ACTH, but not saline, for 1 wk significantly increased adrenal mass, the corticosterone response to ACTH, and the expression of PBR protein and mRNA. Continued ACTH treatment for a second week maintained adrenal mass, steroidogenesis, and PBR mRNA expression. When ACTH was withdrawn after 1 wk and replaced with daily saline injections, however, adrenal mass, ACTH-inducible steroidogenesis, and PBR expression returned to levels comparable to those in age-matched saline controls (i.e. animals that had not received ACTH injections during the first 2 wk). Thus, although ACTH was capable of inducing increased steroidogenic capacity of the juvenile rat adrenal, its effects were only manifest when pups were exposed regularly to high plasma ACTH levels. ACTH, therefore, has significant, but reversible, effects on the development of adrenocortical function, possibly mediated in part by increased expression of PBR.