Effect of Primary Congenital Hypothyroidism upon Expression of Genes Mediating Murine Brain Glucose Uptake

Janine Y. Khan, Rosario A. Rajakumar, Uday P. Devaskar, Lisa A. Weissfeld, Sherin U. Devaskar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)718-725
Number of pages8
JournalPediatric research
Volume45
Issue number5
DOIs
StatePublished - Apr 1999

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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