Thyroid hormones play a major role in the development and function of several 
organs, especially the brain. The actions of thyroid hormones are exerted 
through the interaction of T3 with nuclear receptors and regulation of gene 
expression. The present study analyzed the effects of hypothyroidism and T3 
administration on gene expression in the rat brain and cerebellum during the 
postnatal period. To obtain hypothyroid pups, antithyroid drugs were 
administered to pregnant rats from gestational day 9, and after delivery. T3 was 
administered to the pups, at single daily doses of 5ng/g body weight from 
postnatal day 11 to 15. The pups were sacrificed 24hours after the last 
injection. Hypothyroid neonates showed increased cholesterol levels and 
decreased expression of D1 in liver and of Serca-2 in heart, which were 
normalized with T3 treatment. In the brain, there was decreased expression of 
Ngrn and Rasd2 in the striatum and of the genes encoding sinatotagmin12 (Syt12), 
hairless (Hr), neurotrofina3 (Nt3) and RevErbAα(Nrd1d) in the cerebellum, which 
were also normalized by T3 treatment. These results demonstrate that during the 
postnatal period, T3 reaches the brain and directly influences gene expression 
in this organ. In parallel, we studied the possible actions of a T3 analog, 
Kb430, which in vitro binds preferentially to thyroid receptor α (TRα). This 
compound had no effect on any of the parameters studied. To investigate whether 
the lack of activity of this compound was due to rapid metabolism, we compared 
its activity with that of T3 in T3 receptor transactivation assays using the 
reporter gene chloramphenicol acetyl transferase in Cos7 cells transiently 
expressed through TRα or TRα transfection. The results indicate that Kb430 lacks 
biological activity.