Effect of primary congenital hypothyroidism upon expression of genes mediating murine brain glucose uptake

• Published in: Pediatric research Vol. 45; no. 5; pp. 718 - 725
• Main Authors: KHAN, J. Y, RAJAKUMAR, R. A, DEVASKAR, U. P, WEISSFELD, L. A, DEVASKAR, S. U
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.05.1999
• Subjects: Aging; Amino Acid Substitution; Animals; Animals, Newborn; Biological and medical sciences; Brain - growth & development; Brain - metabolism; Congenital Hypothyroidism; Endocrinopathies; Female; Glucose Transporter Type 1; Glucose Transporter Type 3; Hexokinase - genetics; Hexokinase - metabolism; Hypothyroidism - genetics; Hypothyroidism - metabolism; Male; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Knockout; Monosaccharide Transport Proteins - genetics; Monosaccharide Transport Proteins - metabolism; Nerve Tissue Proteins; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Protein Processing, Post-Translational; Receptors, Thyrotropin - genetics; Receptors, Thyrotropin - metabolism; RNA Processing, Post-Transcriptional; Thyroid. Thyroid axis (diseases); Endocrinopathy; Animal model; Nervous system diseases; Pathophysiology; Enzyme; Pathogenesis; Transferases; Biological transport; Rodentia; Thyroid diseases; Glucose; Gene expression; Hypothyroidism; Blood brain barrier; Congenital disease; Uptake; Hexokinase; Vertebrata; Mammalia; Mouse; Primary; Complication; Neurological disorder; Carrier protein
• ISSN: 0031-3998; 1530-0447
• DOI: 10.1203/00006450-199905010-00019

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.