Thyroid hormone regulates Gαi1 gene expression in the rat cerebellar cortex during post-natal development

Abstract

Thyroid hormone regulates the expression of G protein in tissues such as fat and heart. In the brain, very little information is available relative to the regulation by thyroid hormone of G proteins. Here, we show that the expression of the Gαi1 gene is induced by thyroid hormones in the rat cerebellum during development. Hence, the levels of Gαi1 transcripts and protein were decreased in the cerebellum of hypothyroid neonates. In situ hybridization studies showed that the neurons of the cerebellar cortex, particularly Purkinje cells, were affected. Surprisingly, and in contrast with the in vivo stimulatory effect described above, thyroid hormone repressed the activity of the rat Gαi1 promoter in vitro, suggesting that the effect of this hormone in the cerebellum is indirect. In this regard, we present data suggesting that the transcription factor C/EBPβ could be implicated. First, there are active CEBP binding sites in the Gαi1 promoter. Second, we have found a diminished DNA binding activity of hypothyroid nuclear proteins to a Gαi1 promoter sequence containing a C/EBP binding site. Third, this complex is likely to contain C/EBPβ protein as it is displaced by specific anti-C/ EBPβ antibodies. Finally, there is a significant decrease in the C/EBPβ protein content in the hypothyroid cerebellar cortex.