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

Abstract

The effect of aldosterone on insulin receptor (IR) expression was investigated in U-937 human promonocytic cells. The putative involvement of the mineralocorticoid receptor (MR) was also analysed. Aldosterone binding assays indicated the presence of MRs with high affinity and limited capacity in these cells. RNA blot assays showed that aldosterone treatment decreased the levels of the two major IR mRNAs (11 and 8.5 kb) present in these cells in a dose- and time-dependent manner. The partial reversal of such a decrease by the mineralocorticoid antagonist spironolactone suggested that MR was involved in the process. Experiments with the RNA synthesis inhibitor actinomycin D indicated that the decrease in IR mRNA content in aldosterone-treated cells was not the result of transcript destabilisation. The inhibitory action of aldosterone was not prevented by the simultaneous presence of the protein synthesis inhibitor cycloheximide, suggesting that the reduction of IR gene expression occurs as a direct response to the action of aldosterone. Furthermore, insulin binding assays showed that aldosterone decreased IR capacity but did not alter receptor affinity. In addition, the IR turnover resulted unaltered. These results provide the first evidence for an in vitro modulation of human IR expression by aldosterone.