Postnatal changes of steroid receptor coactivator-1 immunoreactivity in rat cerebellar cortex.

Steroid receptor coactivator-1 (SRC-1) interacts with nuclear hormone receptors (NRs) to mediate their action in a ligand-dependent manner. Among such ligands, thyroid hormone (TH) is particularly crucial for brain development. The expression of many TH target genes is regulated by TH only for a limited critical period, although TH receptor (TR) expression is not greatly altered after such period. To alter TH sensitivity, other factors may be involved. We thus examined the changes in SRC-1 expression during postnatal development in the rat cerebellum by immunohistochemistry and Western blotting. Strong SRC-1 immunoreactivity (IR) was constantly seen in Purkinje cell from postnatal days (P) 2 to P30. SRC-1 IR was also constantly observed in the internal granule cell layer. However, it was negative in the external granule cell layer at P2 and P7, whereas a weak IR was detected in the premigratory zone at P15. SRC-1 IR was detected in the molecular layer after P15. These results indicate that although TR is almost ubiquitously expressed in the developing cerebellum, the TH sensitivity could vary in each subset of cells. By Western blotting, SRC-1 protein level was greatest at P15, at which time TH action may be obvious. Taken together, the differential expression of SRC-1 may be crucial in mediating TH action during cerebellar development.