TISSUE-SPECIFIC EXPRESSION OF ALPHA-MESSENGER AND BETA-MESSENGER RIBONUCLEIC-ACID ISOFORMS OF THE HUMAN MINERALOCORTICOID RECEPTOR IN NORMAL AND PATHOLOGICAL STATES

Expression of the mineralocorticoid receptor (MR) is restricted to som e sodium-transporting epithelia and a few nonepithelial target tissues . Determination of the genomic structure of the human MR (hMR) reveale d two different untranslated exons (1 alpha and 1 beta), which splice alternatively into the common exon 2, giving rise to two hMR mRNA isof orms (hMR alpha and hMR beta). We have investigated expression of hMR transcripts in renal, cardiac, skin, and colonic tissue samples by in situ hybridization with exon 1 alpha and 1 beta specific riboprobes, u sing an exon 2 probe as internal control. Specific signals for either exon 1 alpha- and 1 beta-containing mRNAs were detected in typically h MR-expressing cells in all tissues analyzed. hMR alpha and hMR beta we re present in distal tubules of the kidney, in cardiomyocytes, in ente rocytes of the colonic mucosa, and in keratinocytes and sweat glands. Interestingly, although both isoforms appear to be expressed at approx imately the same level, the relative abundance of each message compare d with that of exon a-containing mRNA strikingly differs among aldoste rone target tissues, suggesting the possibility of other tissue-specif ic transcripts originating from alternative splicing. Finally, functio nal hypermineralocorticism was associated with reduced expression of h MR beta in sweat glands of two patients affected by Conn's and Liddle' s syndrome, whereas normal levels of hMR isoforms were found in one ca se of pseudohypoaldosteronism. Altogether, our results indicate a diff erential, tissue-specific expression of hMR mRNA isoforms, hMR beta be ing down-regulated in situations of positive sodium balance, independe ntly of aldosterone levels.