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 transcriptional activation of a mineralocorticoid response induced by glucocorticoid was generally similar to that of aldosterone, the natural mineralocorticoid hormone. However, compared to aldosterone, glucocorticoid activity decreased when the A/B region of MR was absent. We describe in this study the synthesis and biological activities of seven mutated MRs differently truncated in the N-terminal region. Using transient expression conditions in MCF-7 cells, the N-terminal domain of MR 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 active conformation of MR even in the presence of ligands which are not by themselves able to fully induce such a conformation.
Jausons-Loffreda
N
N
Centre de Recherches Inserm, Montpellier, France.
Chabret
C
C
Pons
M
M
D000450:Aldosterone / Q000494:pharmacology*; D001483:Base Sequence; D002460:Cell Line; D004247:DNA / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D008969:Molecular Sequence Data; D016296:Mutagenesis; D018161:Receptors, Mineralocorticoid / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics; D017384:Sequence Deletion; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection
D018161:Receptors, Mineralocorticoid; D000450:Aldosterone; D003907:Dexamethasone; D004247:DNA; D006854:Hydrocortisone