ROLE OF THE A B REGION OF THE HUMAN MINERALOCORTICOID RECEPTOR IN ALDOSTERONE RESPONSE SELECTIVITY/

In transfection experiments performed with wild-type MR, the maximal t ranscriptional activation of a mineralocorticoid response induced by g lucocorticoid was generally similar to that of aldosterone, the natura l mineralocorticoid hormone. However, compared to aldosterone, glucoco rticoid activity decreased when the A/B region of MR was absent. We de scribe in this study the synthesis and biological activities of seven mutated MRs differently truncated in the N-terminal region. Using tran sient expression conditions in MCF-7 cells, the N-terminal domain of M R has been shown to contain a region (residues 254-390) whose deletion led to an apparent ''aldosterone selectivity''. These results suggest that this region could help to maintain the most transcriptionally ac tive conformation of MR even in the presence of ligands which are not by themselves able to fully induce such a conformation. (C) 1994 Acade mic Press, Inc.