Diurnal Regulation of Glucocorticoid Receptor and Mineralocorticoid Receptor mRNAs in Rat Hippocampus

Abstract

The present studies were undertaken to determine whether hippocampal glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) biosynthesis, as inferred from mRNA expression, exhibit diurnal patterns of activation which may reflect or predict changes in plasma adrenocorticosteroid levels. Animals received either adrenalectomy (ADX) or sham adrenalectomy and were sacrificed at 4-h intervals throughout the diurnal cycle. Hippocampal and control brain areas were assayed for regional GR and MR mRNA changes via semiquantitative in situ hybridization histochemical analysis. The results indicate subfield-specific significant circadian rhythms in both GR and MR mRNAs. A significant diurnal rhythm in GR mRNA expression was seen in the dentate gyrus (DG), which took the shape of a monotonic curve with a marked trough at 1500 h after lights on (1 h after lights off). A similar pattern was evident in subfield CA1, although the effect fell short of statistical significance. No rhythm was seen in CA3. In response to ADX, GR mRNA was markedly increased in both CA1 and CA3; these increases appeared to be independent of circadian influences. In contrast, ADX effects in DG were quite limited and appeared to eliminate the circadian GR mRNA trough. Bimodal diurnal rhythms in MR mRNA expression were observed in all subfields and commonly exhibited troughs at 1500 h after lights on and 0300 h after lights on. These rhythms appeared to be related to circulating steroids, as ADX eliminated both the 1500 and 0300 h troughs, resulting in flat levels of MR mRNA expression corresponding roughly to the circadian peak. Notably, no diurnal GR or MR mRNA rhythms were observed in frontoparietal cortex, nor were any GR mRNA changes seen in the dorsomedial thalamus or hypothalamic paraventricular nucleus. Indeed, ADX was ineffective in altering adrenocorticosteroid receptor mRNA expression in any extrahippocampal region examined. These results indicate that GR and MR mRNAs exhibit hippocampus-specific diurnal rhythms in expression which are controlled to a greater (MR) or lesser (GR) extent by circulating steroids. The apparent steroid sensitivity of hippocampal adrenocorticosteroid receptor populations may be involved in the expression of rhythmic changes in hippocampal function associated with HPA regulation and information processing.