TRANSCRIPTIONAL INDUCTION OF RAT MINERALOCORTICOID RECEPTOR GENE IN NEURONS BY CORTICOSTEROIDS

We investigated the mechanisms by which corticosteroids regulate the expression of the mineralocorticoid receptor (MR) in neurones. Aldosterone and dexamethasone produced a dose-dependent increase of MR mRNA levels in cultured primary hippocampal neurones. Transient transfection of neuroblastoma cells showed that corticosteroids directly activate the rat MR promoter, indicating that the steroid-induced increase in the MR mRNA concentration is at least partially transcriptional. Progressive 5' deletions of the MR promoter sequence revealed that the promoter induction cannot be assigned to a single element. An oligonucleotide comprising a consensus half-glucocorticoid responsive element located at -319 bp in the MR promoter stimulated the corticosteroid-induced activation of the heterologous promoter. Cloning three of these enhancers in tandem greatly potentiated the responses to glucocorticoids and mineralocorticoids, suggesting that although this element is a weak enhancer it can, in combination with other enhancer elements, induce MR gene expression by both types of corticosteroid receptors.