Endocrinology, Vol 133, 2344-2350, Copyright © 1993 by Endocrine Society

ARTICLES

5'-Heterogeneity of the mineralocorticoid receptor messenger ribonucleic acid: differential expression and regulation of splice variants within the rat hippocampus

SP Kwak, PD Patel, RC Thompson, H Akil and SJ Watson
Department of Biological Chemistry, University of Michigan, Ann Arbor 48109-0720.

The mineralocorticoid receptor (MR) cDNA we previously isolated from the rat hippocampus differs from the clone isolated from the kidney at the 5'-untranslated (5'UT) region. The kidney clone (alpha MR mRNA) and the hippocampal clone (beta MR mRNA) possess unique 5'UT sequences of 220 and 300 nucleotides, respectively, but share an invariant peptide- coding domain and appear to encode an identical MR protein. The two mRNA variants may represent tissue-specific forms of the MR or may be coexpressed in the rat hippocampus along with other 5'UT variants. Here, we report that three mRNA subtypes were found in the hippocampus; their relative abundance was as follows: alpha = beta >> gamma. The three mRNA variants were differentially distributed within the hippocampal subfields, with the alpha form being highly enriched in CA2, dentate, the fasciculum cinereum, and the indusium griseum, whereas beta and gamma forms were evenly distributed through CA1-4. Adrenalectomy selectively increased alpha MR mRNA content, but the changes were restricted to CA1, CA2, and CA3 regions. We conclude that multiple MR mRNAs are differentially expressed in the rat hippocampus. The expression of alpha MR mRNA is specifically increased during adrenalectomy, suggesting that the increase in total MR mRNA content documented previously arises from a substantial increase in a single MR variant that elevates the total MR mRNA content, with the apparent elevation reflecting the average of regulated and unregulated transcripts. It is suggested from our data that a complex mechanism involving transcription and translation regulates MR expression in the rat hippocampus.

This article has been cited by other articles:

				J. B Pippal and P. J Fuller Structure-function relationships in the mineralocorticoid receptor J. Mol. Endocrinol., December 1, 2008; 41(6): 405 - 413. [Abstract] [Full Text] [PDF]

				S. A. Reini, C. E. Wood, E. Jensen, and M. Keller-Wood Increased maternal cortisol in late-gestation ewes decreases fetal cardiac expression of 11beta-HSD2 mRNA and the ratio of AT1 to AT2 receptor mRNA Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2006; 291(6): R1708 - R1716. [Abstract] [Full Text] [PDF]

				J. D Turner and C. P Muller Structure of the glucocorticoid receptor (NR3C1) gene 5' untranslated region: identification, and tissue distribution of multiple new human exon 1 J. Mol. Endocrinol., October 1, 2005; 35(2): 283 - 292. [Abstract] [Full Text] [PDF]

				L. Pascual-Le Tallec and M. Lombes The Mineralocorticoid Receptor: A Journey Exploring Its Diversity and Specificity of Action Mol. Endocrinol., September 1, 2005; 19(9): 2211 - 2221. [Abstract] [Full Text] [PDF]

				A. I Freeman, H. L Munn, V. Lyons, A. Dammermann, J. R Seckl, and K. E Chapman Glucocorticoid down-regulation of rat glucocorticoid receptor does not involve differential promoter regulation J. Endocrinol., November 1, 2004; 183(2): 365 - 374. [Abstract] [Full Text] [PDF]

				A.-M. Samuelsson, I. Ohrn, J. Dahlgren, E. Eriksson, B. Angelin, B. Folkow, and A. Holmang Prenatal Exposure to Interleukin-6 Results in Hypertension and Increased Hypothalamic-Pituitary-Adrenal Axis Activity in Adult Rats Endocrinology, November 1, 2004; 145(11): 4897 - 4911. [Abstract] [Full Text] [PDF]

				S. K. Droste, A. Gesing, S. Ulbricht, M. B. Muller, A. C. E. Linthorst, and J. M. H. M. Reul Effects of Long-Term Voluntary Exercise on the Mouse Hypothalamic-Pituitary-Adrenocortical Axis Endocrinology, July 1, 2003; 144(7): 3012 - 3023. [Abstract] [Full Text] [PDF]

				B. A. Kalman and R. L. Spencer Rapid Corticosteroid-Dependent Regulation of Mineralocorticoid Receptor Protein Expression in Rat Brain Endocrinology, November 1, 2002; 143(11): 4184 - 4195. [Abstract] [Full Text] [PDF]

				J. D. Stockand New ideas about aldosterone signaling in epithelia Am J Physiol Renal Physiol, April 1, 2002; 282(4): F559 - F576. [Abstract] [Full Text] [PDF]

				M.-C. Zennaro, A. Souque, S. Viengchareun, E. Poisson, and M. Lombes A New Human MR Splice Variant Is a Ligand-Independent Transactivator Modulating Corticosteroid Action Mol. Endocrinol., September 1, 2001; 15(9): 1586 - 1598. [Abstract] [Full Text] [PDF]

				J. A. McCormick, V. Lyons, M. D. Jacobson, J. Noble, J. Diorio, M. Nyirenda, S. Weaver, W. Ester, J. L. W. Yau, M. J. Meaney, et al. 5'-Heterogeneity of Glucocorticoid Receptor Messenger RNA Is Tissue Specific: Differential Regulation of Variant Transcripts by Early-Life Events Mol. Endocrinol., April 1, 2000; 14(4): 506 - 517. [Abstract] [Full Text]

				J. P. Herman, S. J. Watson, and R. L. Spencer Defense of Adrenocorticosteroid Receptor Expression in Rat Hippocampus: Effects of Stress and Strain Endocrinology, September 1, 1999; 140(9): 3981 - 3991. [Abstract] [Full Text]

				M. E Ullian The role of corticosteroids in the regulation of vascular tone Cardiovasc Res, January 1, 1999; 41(1): 55 - 64. [Full Text] [PDF]

				D. M. Vazquez, J. F. Lopez, M. I. Morano, S. P. Kwak, S. J. Watson, and H. Akil {alpha}, {beta}, and {gamma} Mineralocorticoid Receptor Messenger Ribonucleic Acid Splice Variants: Differential Expression and Rapid Regulation in the Developing Hippocampus Endocrinology, July 1, 1998; 139(7): 3165 - 3177. [Abstract] [Full Text] [PDF]

				E. R. de Kloet, E. Vreugdenhil, M. S. Oitzl, and M. Joëls Brain Corticosteroid Receptor Balance in Health and Disease Endocr. Rev., June 1, 1998; 19(3): 269 - 301. [Abstract] [Full Text]

				M. C. Holmes, K. L. French, and J. R. Seckl Dysregulation of Diurnal Rhythms of Serotonin 5-HT2C and Corticosteroid Receptor Gene Expression in the Hippocampus with Food Restriction and Glucocorticoids J. Neurosci., June 1, 1997; 17(11): 4056 - 4065. [Abstract] [Full Text] [PDF]

				M.-C. Zennaro, N. Farman, J.-P. Bonvalet, and M. Lombes Tissue-Specific Expression of {alpha} and {beta} Messenger Ribonucleic Acid Isoforms of the Human Mineralocorticoid Receptor in Normal and Pathological States J. Clin. Endocrinol. Metab., May 1, 1997; 82(5): 1345 - 1352. [Abstract] [Full Text] [PDF]

				M.-C. Zennaro, M.-C. Keightley, Y. Kotelevtsev, G. S. Conway, F. Soubrier, and , P. J. Fuller Human Mineralocorticoid Receptor Genomic Structure and Identification of Expressed Isoforms J. Biol. Chem., September 8, 1995; 270(36): 21016 - 21020. [Abstract] [Full Text] [PDF]