LONG-TERM SELECTIVE DOWN-REGULATION OF BRAIN GLUCOCORTICOID RECEPTORSAFTER NEONATAL DEXAMETHASONE TREATMENT IN RATS

The development of corticosteroid receptors may be permanently modifie d 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 t wo more times on PND 3 and 5 in several brain areas. [H-3]Corticostero ne (CORT) binding capacity (B-max) and affinity (K-d) were determined at 3 weeks old and adult ages by using saturation analysis. The minera locorticoid type receptor (MR) and the glucocorticoid receptor (GR) si tes were measured separately with single point analysis applying a sel ective glucocorticoid ligand RU 28362 saturating GR. The decrease in C ORT binding was due to a selective GR decrement in all structures and tile MR concentration was not changed considerably. The basal levels o f plasma CORT were not permanently influenced by neonatal DEX. In conc lusion, 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.