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 evid ence suggest that a reduction in insulin-like growth factor-I (IGF-I) expre ssion and/or action has a role. To assess whether reduced IGF-I expression and/or actions mediates the brain pathology of congenital hypothyroidism, w e 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 IG F-l mRNA express ion was assessed in the cerebral cortex and cerebellum by ribonuclease prot ection assay. To control for mRNA loading, the signal of IGF-I protected ba nds was normalized to those for cyclophillin. IGF-I mRNA expression in hypo thyroid animals was decreased significantly in cortex at P10 and P14(42 and 60%, respectively). In the cerebellum, IGF-I mRNA expression was down-regu lated at all ages studied, but the decrease was only statistically signific ant at P7 (31% decreased). We conclude that hypothyroidism alters IGF-I exp ression in the developing brain. Furthermore, we speculate that IGF-I plays a role in mediating some thyroid hormone actions during brain development. (C) 2000 Published by Elsevier Science Ireland Ltd.