Abstract
In the developing rat cerebrum, the level of different isoforms of Na-K-ATPase mRNA increases significantly during the first three postnatal weeks, which represent the critical period of synaptogenesis and myelination—the two thyroid hormone-sensitive maturational events. To determine the possible functional relationship of these isoforms with maturational events in the developing brain and their mode of regulation by T3, we have examined the effect of hypothyroidism on the expression of the different α-isoforms (α1, α2, and α3) of Na-K-ATPase mRNA covering the first 3 wk of postnatal development. Quantitation of these mRNAs from cerebra of 1-, 5-, 10-, 15-, and 20-d-old normal and hypothyroid rats by Northern blot analysis indicate that α3 mRNA is not only predominantly expressed throughout this entire period of study but also represents the species which is most severely affected in the hypothyroid brain. The relative sensitivity for the expression of these mRNAs to T3 were α3>α1>α2. These results, together with the report of predominant expression of the α3 isoform in neuronal cells, suggest specific functional involvement of this isoform with the decisive maturational events in the rat brain. Kinetic studies on in vivo induction of Na-K-ATPase α-mRNAs by T3 in the 15-d-old hypothyroid rat shows clear stimulation of all the isoforms within 1 h of the administration of the optimal dose (200 µg T3/100 g body wt) suggesting a direct, possibly transcriptional effect of the hormone on the expression of these genes.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Chaudhury S., Ismail-Beigi F., Gick G. G., Levenson R., and Edelman I. S. (1987) Effect of thyroid hormone on the abundance of Na-K-adenosine triphosphatase α-subunit messenger ribonucleic acid.Mol. Endocrinol. 1, 83–89.
Chomczynski P. and Sacchi N. (1987) Single step method of RNA isolation by acid guanidium thiocyanate phenol chloroform extraction.Anal. Biochem. 162, 156–159.
Corthesy-Theulaz I., Merillat A. M., Honegger P., and Rossier B. C. (1990) Na+-K+-ATPase gene expression during in vitro development of rat fetal forebrain.Am. J. Physiol. 258, C1062-C1069.
Corthesy-Theulaz I., Merillat A. M., Honegger P., and Rossier B. C. (1991) Differential regulation of Na-K-ATPase isoform gene expression by T3 during rat brain development.Am. J. Physiol. 261, C124-C131.
Feinberg A. P. and Vogelstein B. (1983) A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity.Anal. Biochem. 132, 6–13.
Feng J., Orlowski J., and Lingrel J. B. (1993) Identification of a functional thyroid hormone response element in the upstream flanking region of the human Na-K-ATPase β1 gene.Nucleic Acids Res. 21, 2619–2626.
Gick G. G., Ismail-Beigi F., and Edelman I. S. (1988) Thyroidal regulation of rat renal and hepatic Na-K-ATPase gene expression.J. Biol. Chem. 263, 16,610–16,618.
Good P. J., Richter K., and David J. B. (1990) A nervous system specific isotype of the β-subunit of Na-K-ATPase expressed during early development ofXenopus laevis.Proc. Natl. Acad. Sci. USA 87, 9088–9092.
Martin Vasallo P., Dackowski W., Emanuel J. R., and Levenson R. (1989) Identification of a putative isoform of Na-K-ATPase β-subunit.J. Biol. Chem. 264, 4614–4618.
McGrail K. M., Philip J. M., and Sweadner K. J. (1991) Immunofluorescent localization of three Na-K-ATPase isozymes in the rat central nervous system both neurons and glia can express more than one Na-K-ATPase.J. Neuroscience 11, 381–391.
Melikian J. and Ismail-Beigi F. (1991) Thyroid hormone regulation of Na-K-ATPase subunit mRNA expression in neonatal rat myocardium.J. Membrane Biol. 119, 171–177.
Orlowski J. and Lingrel J. B. (1988) Tissue specific and developmental regulation of rat Na-K-AT-Pase catalytic α-isoform and β-subunit mRNAs.J. Biol. Chem. 263, 10,436–10,444.
Pathak B. G., Pugh D. G., and Lingrel J. B. (1990) Characterization of the 5′ flanking region of the human and rat Na-K-ATPase α3 gene.Genomics 8, 641–647.
Pipaon C., Santos A., and Perez-Castillo A. (1992) Thyroid hormone regulates NGF1-A gene expression in rat brain during development.J. Biol. Chem. 267, 21–23.
Poddar R., Paul S., Chaudhury S., and Sarkar P. K., (1996) Regulation of actin and tubulin gene expression by thyroid hormone during rat brain development.Mol. Brain Res. 35, 111–118.
Rabierre A. and Legrand J. (1972) Donnees quantitatives sur la synaptogenese dans de cervelet du rat normal et rendu hypothyroidien per le propylthiouracile.C. R. Acad. Sci. Paris277, 3581–3584.
Schmitt C. A. and McDonough A. A. (1986) Developmental and thyroid hormone regulation of two molecular forms of Na+-K+-ATPase in brain.J. Biol. Chem. 261, 10,439–10,444.
Schmitt A. and McDonough A. A. (1988) Thyroid hormone regulates α and α+ isoforms of Na-K-ATPase during development in neonatal rat brain.J. Biol. Chem. 263, 17,643–17,649.
Schneider J. W., Mercer R. W., Gilmore Hebert M., Utset M. F., Lai C., Greene H., and Benz E. J. Jr. (1988) Tissue specificity localization in brain and cell free translation of mRNA coding the A3 isoform of Na+-K+-ATPase.Proc. Natl. Acad. Sci. USA. 85, 284,285.
Shull G. E., Greeb J., and Lingrel J. B. (1987) Molecular cloning of three distinct forms of the Na+-K+-ATPase α-subunit from rat brain.Biochemistry 25, 8125–8132.
Schwartz H. I. and Oppenheimer J. H. (1978) Ontogenesis of 3,5,3′-tri-iodo-thyronine receptors in neonatal rat brain—dissociation between receptor concentration and stimulation of oxygen consumption by 3,5,3′-tri-iodothyronine.Endocrinology 103, 943–948.
Sweadner K. J., McGrail K. M., and Khaw B. A. (1992) Discoordinate regulation of isoforms of Na-K-ATPase and myosin heavy chain.J. Biol. Chem. 267, 769–771.
Yagawa Y., Kawakami K., and Nagano K. (1990) Cloning and analysis of the 5′-flanking region of rat Na-K-ATPase α1 subunit gene.Biochem. Biophys. Acta 1049, 286–292.
Young R. M. and Lingrel J. B. (1987) Tissue distribution of mRNAs encoding the α-isoforms and β-subunit of rat Na+-K+-ATPase.Biochem. Biophys. Res. Commun. 145, 52–58.
Young R. M., Shull G. E., and Lingrel J. B. (1987) Multiple mRNAs of rat kidney and brain encode a single Na+-K+-ATPase β-subunit protein.J. Biol. Chem. 262, 4905–4910.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Chaudhury, S., Bajpai, M. & Bhattacharya, S. Differential effects of hypothyroidism on Na-K-ATPase mRNA α isoforms in the developing rat brain. J Mol Neurosci 7, 229–234 (1996). https://doi.org/10.1007/BF02736843
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02736843