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.