Type I and Type II corticosteroid receptor gene expression in the rat: Effect of adrenalectomy and dexamethasone administration

Abstract

We have used 32P-labeled cRNA probes directed against Type I (mineralocorticoid, high affinity glucocorticoid) and Type II (classical glucocorticoid) receptor mRNA to screen various tissues, and have investigated the effect of adrenalectomy (ADX) and dexamethasone (DM) administration on their levels in hippocampus. Both Northern blot and S1 nuclease analysis showed Type I mRNA to be high in hippocampus, colon, and heart; low in liver; and undetectable in thymus. Type II mRNA was high in liver, thymus, and brain; and low in testis and parotid. A transient increase in both hippocampal Type I and Type II mRNA was noted at 1-3 days post ADX. DM similarly elicited a rise in hippocampal Type I mRNA at 2-4 days after ADX, but prevented the ADX-induced increment in Type II mRNA. In contrast to the transient increase in Type I receptor mRNA levels, hippocampal levels of Type I receptors measured by [3H]aldosterone binding were constant 1-16 days post ADX. DM administration caused a doubling in Type I receptor levels over 4 days, with plateau levels at 4-16 days; previously, DM has been shown to lower Type II receptor levels in the hippocampus. We interpret these data in physiological terms as suggesting 1) that Type I receptor transcription in the hippocampus may be negatively regulated by corticosterone occupying Type I receptors, given the effect of ADX on message levels; 2) that Type II receptor synthesis in the hippocampus may be negatively regulated by corticosterone occupying Type II receptors, given the opposing effects of ADX and DM; and 3) that the efficiency of Type I mRNA translation, and/or the stability of Type I receptors, are elevated after chronic occupancy of type II receptors by administered DM.