Effect of primary congenital hypothyroidism upon expression of genes mediating murine brain glucose uptake.
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.
Khan
J Y
JY
Department of Pediatrics, University of Pittsburgh School of Medicine, PA 15213, USA.
Rajakumar
R A
RA
Devaskar
U P
UP
Weissfeld
L A
LA
Devaskar
S U
SU
D000375:Aging; D019943:Amino Acid Substitution; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D003409:Congenital Hypothyroidism; D005260:Female; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D006593:Hexokinase / Q000235:genetics / Q000378:metabolism*; D007037:Hypothyroidism / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D011499:Protein Processing, Post-Translational; D012323:RNA Processing, Post-Transcriptional; D011989:Receptors, Thyrotropin / Q000235:genetics* / Q000378:metabolism
D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D009004:Monosaccharide Transport Proteins; D009419:Nerve Tissue Proteins; D011989:Receptors, Thyrotropin; C495678:Slc2a1 protein, mouse; C495689:Slc2a3 protein, mouse; D006593:Hexokinase