Gene array analysis of the effects of chronic adrenocorticotropic hormone in vivo on immature rat adrenal glands

Development of a mature adrenocortical phenotype is a critical event in the transition of mammals from fetal to postnatal life. We previously reported that the functional maturation of the adrenal glands of newborn rats is accelerated by adrenocorticotropic hormone (ACTH). We report here that chronic exposure of neonatal/juvenile rat pups to ACTH in vivo results in significant changes in expression of over 200 genes in the adrenal glands. ACTH significantly upregulated genes associated with cell signaling, gene transcription, cell migration and tissue remodeling. In addition, ACTH significantly downregulated several genes associated with de novo cholesterol biosynthesis and cholesterol trafficking. Finally, ACTH upregulated genes associated with intracellular metabolism and inactivation of glucocorticoids. The results demonstrate that the developmental effects of ACTH alter expression of a broad range of genes involved not solely in steroid synthesis, but in cellular functions related to growth and differentiation of the glands. In addition, the negative effects of ACTH on genes required for cholesterol synthesis and production of active glucocorticoids, suggests a mechanism whereby excessive production of glucocorticoids, which may have deleterious actions on developing structures like the central nervous system, is prevented.