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Tissue-Specific Expression of and ß Messenger Ribonucleic Acid Isoforms of the Human Mineralocorticoid Receptor in Normal and Pathological States

INSERM U 246, Institut Féderatif de Recherche Cellules Epithéliales, Faculté de Médecine Xavier Bichat (M-C.Z., N.F., J-P.B., M.L.), 75870 Paris Cedex 18, France; and Clinica di Endocrinologia, Università degli Studi di Ancona, Ospedale Regionale di Torrette (M-C.Z.), 60100 Ancona, Italy

Address all correspondence and requests for reprints to: Marc Lombès, INSERM U 246, Institut Féderatif de Recherche Cellules Epithéliales, Faculté de Médecine Xavier Bichat, 16, rue Henri Huchard, BP416, 75870 Paris Cedex 18, France. E-mail: mlombes{at}bichat.inserm.fr

Expression of the mineralocorticoid receptor (MR) is restricted to some sodium-transporting epithelia and a few nonepithelial target tissues. Determination of the genomic structure of the human MR (hMR) revealed two different untranslated exons (1 and 1ß), which splice alternatively into the common exon 2, giving rise to two hMR mRNA isoforms (hMR and hMRß). We have investigated expression of hMR transcripts in renal, cardiac, skin, and colonic tissue samples by in situ hybridization with exon 1 and 1ß specific riboprobes, using an exon 2 probe as internal control. Specific signals for either exon 1- and 1ß-containing mRNAs were detected in typically hMR-expressing cells in all tissues analyzed. hMR and hMRß were present in distal tubules of the kidney, in cardiomyocytes, in enterocytes of the colonic mucosa, and in keratinocytes and sweat glands. Interestingly, although both isoforms appear to be expressed at approximately the same level, the relative abundance of each message compared with that of exon 2-containing mRNA strikingly differs among aldosterone target tissues, suggesting the possibility of other tissue-specific transcripts originating from alternative splicing. Finally, functional hypermineralocorticism was associated with reduced expression of hMRß in sweat glands of two patients affected by Conn’s and Liddle’s syndrome, whereas normal levels of hMR isoforms were found in one case of pseudohypoaldosteronism. Altogether, our results indicate a differential, tissue-specific expression of hMR mRNA isoforms, hMRß being down-regulated in situations of positive sodium balance, independently of aldosterone levels.

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