Objective:To observe the effect of thyroid hormones on 11?-hydroxysteroid dehydrogenase type 1(11?-HSD1) in newborn rats' hippocampus. Methods: Hypothyroid model was induced with propylthiouracil(PTU, 50 mg/d) in SD rats in the last week of pregnancy and was confirmed by measuring the levels of thyroid hormones and thyrotropin(TSH) in the newborn rats' blood. Western blot was used to determine the expression of 11?-HSD1 in hippocampus in newborn rats. Effects of triiodothyronine(T 3) and synthetic glucocorticoid dexamethasone(Dex) on expression of 11?-HSD1 in primarily- cultured hippocampus were studied with thin layer chromatography(TLC) and Western blot. Results: Thyroid hormone levels decreased and TSH level increased in the newborn rats' blood. The expression of 11?-HSD1 decreased by 41.6% in the hippocampus of newborn rats born to the mothers treated with PTU. T 3(10 -9 ,10 -8 ,10 -7 mol/L) and Dex(10 -7 mol/L) up-regulated the activity of 11?-HSD1 by 29.4%,45.6%,60.9% and 39.8%,respectively. T 3(10 -9 ,10 -8 ,10 -7 mol/L) and Dex(10 -7 mol/L) increased the expression of 11?-HSD1 protein by 26.0%,43.2%,64.9% and 41.1%,respectively.Synergistic effect of T 3 and DEX was observed in terms of regulating 11?-HSD1: the expression of 11?-HSD1 increased by 123.3% in the hippocampal neurons exposed to both Dex(10 -7 mol/L) and T 3 (10 -7 mol/L) and the activity increased by 114.1%. Conclusion:Thyroid hormone can up-regulate the expression of 11?-HSD1 in the hippocampus during brain maturation either by itself or synergistically with glucocorticoid, thereby enhancing the action of glucocorticoids on the brain.

The pathologic changes of cerebral tissues in hypothyroidism and the molecular mechanism of brain development influenced by lower thyroid hormone levels are reviewed.