Effects of hypothyroidism on insulin-like growth factor-I expression during brain development in mice.
Hypothyroidism has devastating consequences on brain development. While the mechanisms that mediate these effects are not known, several lines of evidence suggest that a reduction in insulin-like growth factor-I (IGF-I) expression and/or action has a role. To assess whether reduced IGF-I expression and/or actions mediates the brain pathology of congenital hypothyroidism, we induced hypothyroidism by treating pregnant mice and lactating dams with 0. 1% propylthiouracil (PTU) in drinking water. Control and PTU-treated pups were sacrificed on postnatal day (P) 7, 10 and 14, and IGF-I mRNA expression was assessed in the cerebral cortex and cerebellum by ribonuclease protection assay. To control for mRNA loading, the signal of IGF-I protected bands was normalized to those for cyclophillin. IGF-I mRNA expression in hypothyroid animals was decreased significantly in cortex at P10 and P14 (42 and 60%, respectively). In the cerebellum, IGF-I mRNA expression was down-regulated at all ages studied, but the decrease was only statistically significant at P7 (31% decreased). We conclude that hypothyroidism alters IGF-I expression in the developing brain. Furthermore, we speculate that IGF-I plays a role in mediating some thyroid hormone actions during brain development.
Elder
D A
DA
Department of Pediatrics, Division of Endocrinology, CB 7220, 108 Burnett-Womack, The University of North Carolina at Chapel Hill, NC 27599-7220, Chapel Hill, USA.
Karayal
A F
AF
D'Ercole
A J
AJ
Calikoglu
A S
AS
D000818:Animals; D001921:Brain / Q000254:growth & development* / Q000503:physiopathology*; D002531:Cerebellum / Q000378:metabolism / Q000503:physiopathology; D002540:Cerebral Cortex / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D007037:Hypothyroidism / Q000378:metabolism* / Q000503:physiopathology; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D013963:Thyroid Hormones / Q000378:metabolism
D012333:RNA, Messenger; D013963:Thyroid Hormones; D007334:Insulin-Like Growth Factor I