REGULATION OF GLUCOCORTICOID AND MINERALOCORTICOID RECEPTOR MESSENGER-RNAS IN THE HIPPOCAMPUS OF THE MATERNALLY DEPRIVED INFANT RAT

The hypothalamic-pituitary-adrenal (HPA) axis in the developing rat ha s a limited response to acute challenges between days 3 and 14 of life . Several hypotheses have been proposed to explain this quiescent stat e. Immaturity of brain, pituitary and adrenal elements or excessive fe edback inhibition are common explanations. Recently, a series of studi es by Levine and co-workers has shown that prolonged maternal deprivat ion (24 h) results in increased basal and stress induced corticosteron e (CS) levels. An increased adrenal response to ACTH along with an enh anced and sustained ACTH response have been implicated in this phenome non. A brain structure that appears to be important for normal HPA fun ction is the hippocampus, a structure rich in corticosteroid receptors , which has been hypothesized to play a role in the basal tone of the HPA and in the magnitude and duration of stress responses. Thus, to st udy further the possible mechanisms leading to an enhanced and sustain ed ACTH response that is seen in maternally deprived pups, we used in situ hybridization to investigate hippocampal mineralocorticoid (MR) a nd glucocorticoid receptor (GR) gene expression in 12 groups of animal s: six groups involved 24 h maternally deprived (DEP) and non-deprived (NDEP) rat pups at three ages (6-, 9-, and 12-days-old); the other si x groups included pups similarly treated, but challenged with an expos ure to a mild stressor (saline injection) and sacrificed 1 h thereafte r. We found: (1) an age effect for almost every hippocampal subfield f or both MR and GR mRNAs: MR increases with age, while GR decreases; (2 ) down-regulation of MR mRNA in CA1 region in the DEP animals; and (3) down-regulation of GR mRNA, also in CA1, in the saline-injected DEP a nd NDEP animals. Our results indicate that corticoid receptors in the developing CA1 hippocampal region appear to be sensitive to circulatin g CS. They also suggest that the relative ratio of GR and MR in the CA 1 region may contribute to the enhanced and sustained CS response seen after a mild stressor in deprived animals.