Long-term selective down-regulation of brain glucocorticoid receptors after neonatal dexamethasone treatment in rats

The development of corticosteroid receptors may be permanently modified by perinatal hormonal influences. Changes in binding characteristics of corticosteroid receptors were examined in rats treated sc. with 1 mu g/g dexamethasone (DEX) on postnatal day (PND) 1 and subsequently two more times on PND 3 and 5 in several brain areas. [H-3]Corticosterone (CORT) binding capacity (B-max) and affinity (K-d) were determined at 3 weeks old and adult ages by using saturation analysis. The mineralocorticoid type receptor (MR) and the glucocorticoid receptor (GR) sites were measured separately with single point analysis applying a selective glucocorticoid ligand RU 28362 saturating GR. The decrease in CORT binding was due to a selective GR decrement in all structures and the MR concentration was not changed considerably. The basal levels of plasma CORT were not permanently influenced by neonatal DEX. In conclusion, DEX given during the first week of life resulted in long-term and selective down-regulation of GR and this decrement was independent of the actual circulating CORT level.