Inhibition by aldosterone of insulin receptor mRNA levels and insulin binding in U-937 human promonocytic cells

The effect of aldosterone on insulin receptor (IR) expression was investiga ted in U-937 human promonocytic cells. The putative involvement of the mine ralocorticoid receptor (MR) was also analysed. Aldosterone binding assays i ndicated the presence of MRs with high affinity and limited capacity in the se cells. RNA blot assays showed that aldosterone treatment decreased the l evels of the two major IR mRNAs (II and 8.5 kb) present in these cells in a dose- and time-dependent manner. The partial reversal of such a decrease b y the mineralocorticoid antagonist spironolactone suggested that MR was inv olved in the process. Experiments with the RNA synthesis inhibitor actinomy cin D indicated that the decrease in IR mRNA content in aldosterone-treated cells was not the result of transcript destabilisation. The inhibitory act ion of aldosterone was not prevented by the simultaneous presence of the pr otein synthesis inhibitor cycloheximide, suggesting that the reduction of I R gene expression occurs as a direct response to the action of aldosterone. Furthermore, insulin binding assays showed that aldosterone decreased IR c apacity but did not alter receptor affinity. In addition, the IR turnover r esulted unaltered. These results provide the first evidence for an in vitro modulation of human IR expression by aldosterone. (C) 1999 Elsevier Scienc e Ltd. All rights reserved.