Abstract
Using hyt/hyt mice that exhibit naturally occurring primary hypothyroidism (n = 72) and Balb/c controls (n = 66), we examined the mRNA, protein, and activity of brain glucose transporters (Glut 1 and Glut 3) and hexokinase I enzyme at various postnatal ages (d 1, 7, 14, 21, 35, and 60). The hyt/hyt mice showed an age-dependent decline in body weight (p < 0.04) and an increase in serum TSH levels (p < 0.001) at all ages. An age-dependent translational/posttranslational 40% decline in Glut 1 (p = 0.02) with no change in Glut 3 levels was observed. These changes were predominant during the immediate neonatal period (d 1). A posttranslational 70% increase in hexokinase enzyme activity was noted at d 1 alone (p < 0.05) with no concomitant change in brain 2-deoxy-glucose uptake. This was despite a decline in the hyt/hyt glucose production rate. We conclude that primary hypothyroidism causes a decline in brain Glut 1 associated with no change in Glut 3 levels and a compensatory increase in hexokinase enzyme activity. These changes are pronounced only during the immediate neonatal period and disappear in the postweaned stages of development. These hypothyroid-induced compensatory changes in gene products mediating glucose transport and phosphorylation ensure an adequate supply of glucose to the developing brain during transition from fetal to neonatal life.
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Abbreviations
- Glut :
-
glucose transporter
- Hyt/hyt :
-
hypothyroid mouse strain
- TSH :
-
thyroid stimulating hormone
- T4 :
-
thyroxine
- T3 :
-
triiodothyronine
- CGU :
-
cerebral glucose uptake
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Acknowledgements
The authors thank Dr. G. I. Bell (Howard Hughes Institute, University of Chicago, IL) for providing the mouse Glut 3 cDNA and Drs. Schwab and Wilson (Michigan State University, East Lansing, MI) for providing the rat hexokinase I cDNA. The authors also thank Stacy J. Hicks for technical assistance.
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Supported by National Institutes of Health grants HD 33997 and HL 52839, and the Twenty-five Club neonatal research funds, Magee-Womens Hospital, Pittsburgh, PA.Presented in part at the 1997 Society for Pediatric Research Meetings, Washington DC.
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Khan, J., Rajakumar, R., Devaskar, U. et al. Effect of Primary Congenital Hypothyroidism upon Expression of Genes Mediating Murine Brain Glucose Uptake. Pediatr Res 45 (Suppl 5), 718–725 (1999). https://doi.org/10.1203/00006450-199905010-00019
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DOI: https://doi.org/10.1203/00006450-199905010-00019
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