Glucocorticoid receptor translocation and expression of relevant genes in the hippocampus of adolescent and adult male rats

Abstract

We investigated whether pre-pubertal (postnatal day [P] 35) and post-pubertal adolescent (P45) and adult (P75) male rats differed in stressor-induced hormonal responses and in glucocorticoid receptor (GR) translocation because it has been proposed that negative feedback is maturing in adolescence and may be a basis for the prolonged activation of the HPA axis in adolescents compared with adults. The three age groups did not differ at baseline in plasma corticosterone or progesterone concentrations, and P35 had lower concentrations of testosterone than did both P45 and P75 rats, which did not differ. After 30min of restraint stress, plasma concentrations of corticosterone and progesterone increased to a greater extent in the adolescents than in the adults. Whereas restraint stress increased concentrations of testosterone in adult males, concentrations decreased in adolescents. In all three age groups, restraint stress reduced GR expression in the cytosol and increased expression in the nucleus within the hippocampus, and the increase in nuclear GR was greater in pre-pubertal adolescents compared with adults. In a separate set of rats we investigated age differences in hippocampal mRNA expression of corticosteroid receptors (MR and GR) and of chaperones (FKBP5, FKBP4, BAG-1), which are known to modulate their activity, at baseline and after restraint stress. Restraint stress decreased the expression of GR and increased the expression of FKBP5 mRNA, and age was not a significant factor. Higher expression of FKBP4 mRNA was found at P35 than at P75. Most research of HPA function in adolescent rats has involved pre-pubertal rats; the present findings indicate that despite their increase in gonadal function, responses to stressors in P45 rats are more like those of pre-pubertal than adult rats. The greater stressor-induced GR translocation in pre-pubertal adolescents parallels their greater release of corticosterone in response to stressors, which may contribute to the enhanced sensitivity of adolescent rats to the effects of chronic stress exposures compared with adults.