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Aldosterone and thyroid hormone modulation of α1-, β1-mRNA, and Na,K-Pump sites in rabbit distal colon epithelium. Evidence for a novel mechanism of escape from the effect of hyperaldosteronemia

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Summary

Aldosterone and thyroid hormone regulation of Na,K-pump biosynthesis has been examined in the distal colon epithelium of rabbits. Qualitative analysis of α-subunit isoform distribution (α1, α2, α3) detected only the α1-mRNA in the distal colon epithelium and outer renal medulla, while all three isoforms were observed in rabbit brain. A low-sodium diet led to a rise in serum aldosterone from 0.6 nm to 1.4–1.9 nm and an increase of α1-mRNA to 162%, β1-mRNA to 120%, and the number of Na,K-pump units as determined by specific [3H]-ouabain binding to 182% of control by the second day of the diet. While aldosterone levels remained elevated, a spontaneous decrease in serum levels of T3 and T4 to 50–60% of control from the third day of the diet was followed by downregulation of β1-mRNA to 55–67%, α1-mRNA to 63–105%, and of [3H]-ouabain binding to 103% of control, suggesting that a reduced rate of synthesis of the β1-subunit is rate limiting for Na,K-pump biosynthesis. Substitution with T3 (10 μg/kg) at the seventh day with transient restoration of serum T3 to control levels, led to rapid accumulation of β1-mRNA to 152%, of α1-mRNA to 135%, and of the number of Na,K-pump units to 153% of control. This is consistent with thyroid hormone having a permissive role for the aldosterone stimulation of Na,K-pump biosynthesis. Reduced rates of β-subunit transcription due to low thyroid hormone levels appear to provide a mechanism for escape from the effect of hyperaldosteronemia on the number of Na,K-pump units.

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Author notes

  1. Hubert Wiener

    Present address: Department of Pharmacology, University of Vienna, Austria

Authors and Affiliations

  1. Biomembrane Research Centre, August Krogh Institute, Copenhagen University, 2100, Copenhagen OE, Denmark

    Hubert Wiener, Jesper M. Nielsen, Dan A. Klaerke & Peter L. Jørgensen

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  1. Hubert Wiener
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  2. Jesper M. Nielsen
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  3. Dan A. Klaerke
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  4. Peter L. Jørgensen
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Additional information

We thank Dr. J. Lingrel, Department of Molecular Genetics, University of Cincinnati, Cincinnati, Ohio, for the generous gift of α1−, α2−, α3−, and β1-subunit cDNAs. The study was supported by grants from the Danish Medical Research Council, Novo's Foundation and the Carlsberg Foundation.

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Wiener, H., Nielsen, J.M., Klaerke, D.A. et al. Aldosterone and thyroid hormone modulation of α1-, β1-mRNA, and Na,K-Pump sites in rabbit distal colon epithelium. Evidence for a novel mechanism of escape from the effect of hyperaldosteronemia. J. Membarin Biol. 133, 203–211 (1993). https://doi.org/10.1007/BF00232020

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  • DOI: https://doi.org/10.1007/BF00232020

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