T3 strongly regulates GLUT1 and GLUT3 mRNA in cerebral cortex of hypothyroid rat neonates

Experimental hypothyroidism alters the expression of the GLUT1 and GLUT4 glucose transporters in brown adipose tissue, skeletal muscle and heart. Congenital hypothyroidism disrupts the development and function of the CNS, and the importance of GLUT1 for proper brain function has been dramatically evidenced in the cases of GLUT1 deficiency syndrome. Because of this, we hypothesised that the expression of GLUT1 and GLUT3, glucose transporters expressed in brain cortex, may be altered in congenital hypothyroidism. GLUT3 mRNA was induced during postnatal development whereas GLUT1 mRNA was initially repressed and further induced; both processes were essentially similar in control and hypothyroid animals. Under these conditions GLUT1 protein expression was reduced in cerebral cortex from 15-day-old hypothyroid neonates, which suggests the existence of post-transcriptional alterations. The most striking differences were observed when hypothyroid animals at different developmental stages were treated acutely with T3. GLUT1 and GLUT3 mRNA expression behaved in opposite ways in response to treatment with the hormone. Furthermore, the behaviour of each glucose transporter isoform against T3 was not uniform but changed alongside development. In all, our data show that the regulation of GLUT1 and GLUT3 in cerebral cortex is regulated by T3 in a complex way and suggest that alterations in the expression of glucose transporters induced by hypothyroidism might have a functional impact on brain glucose uptake.