Subregion-specific differences in translocation patterns of mineralocorticoid and glucocorticoid receptors in rat hippocampus

Abstract

Corticosteroids exert important effects on brain function via glucocorticoid (GRs) and mineralocorticoid receptors (MRs) by inducing receptor translocation to the nucleus, where the receptor-ligand complexes modulate transcription of target genes. Based on studies describing uneven receptor expression patterns, regionally different corticosterone effects, and the importance of timing of corticosteroid effects, we hypothesized that differential patterns of MR and GR translocation exist in the rat hippocampus in response to a single glucocorticoid stimulus. Temporal patterns of receptor translocation were investigated in both intact and adrenalectomised (ADX) male Sprague-Dawley rats. Animals were sacrificed at different time points after intraperitoneal administration of 3 mg/kg corticosterone. Specific MR and GR primary antibodies were used for immunohistochemistry and confocal microscopy to visualize and quantify receptor subcellular localisation in the different subregions of the hippocampus. Results indicate (1) significant subregion-specific differences in translocation patterns for both MR and GR, with respect to the extent and timing of nuclear translocation and (2) specific differences between ADX and intact animals that are most prominent in the dentate gyrus: while corticosterone given to intact animals induced a marked nuclear increase in both MR and GR, in ADX animals nuclear MR signal was already elevated in the absence of hormone, and did not change after steroid treatment. We conclude that in response to a single stress-like increase in corticosterone distinct region-specific MR- and GR-dependent translocation patterns exist in the rat hippocampus, which may underlie region-specific effects relevant to homeostatic control.