TRANSCRIPTIONAL INDUCTION OF RAT MINERALOCORTICOID RECEPTOR GENE IN NEURONS BY CORTICOSTEROIDS

We investigated the mechanisms by which corticosteroids regulate the e xpression of the mineralocorticoid receptor (MR) in neurones. Aldoster one and dexamethasone produced a dose-dependent increase of MR mRNA le vels in cultured primary hippocampal neurones. Transient transfection of neuroblastoma cells showed that corticosteroids directly activate t he rat MR promoter, indicating that the steroid-induced increase in th e MR mRNA concentration is at least partially transcriptional. Progres sive 5' deletions of the MR promoter sequence revealed that the promot er induction cannot be assigned to a single element. An oligonucleotid e comprising a consensus half-glucocorticoid responsive element locate d at -319 bp in the MR promoter stimulated the corticosteroid-induced activation of the heterologous promoter. Cloning three of these enhanc ers in tandem greatly potentiated the responses to glucocorticoids and mineralocorticoids, suggesting that although this element is a weak e nhancer it can, in combination with other enhancer elements, induce MR gene expression by both types of corticosteroid receptors.