Expression and regulation by thyroid hormone (TH) of zebrafish IGF-I gene and amphioxus IGFl gene with implication of the origin of TH/IGF signaling pathway

Thyroid hormone (TH)/insulin-like growth factor (IGF) signaling pathway has been identified in all the vertebrates, but its evolutionary origin remains elusive. In this study we examined the expression profiles in vitro as well as in vivo of the IGF-I gene of fish Danio rerio (vertebrate) and the IGF-like gene (IGFl) of amphioxus Branchiostoma japonicum (protochordate) following T3 treatment. Our results showed that T3 was able to enhance hepatic IGF-I/IGFl gene expression in vitro in both zebrafish and amphioxus in a dose-dependent manner. This T3-induced hepatic expression of IGF-I/IGFl genes in both species was significantly inhibited by the T3-specific inhibitor DEA, indicating the specificity of IGF-I/IGFl gene regulation by T3. At 100 nM T3, in both the long (42 h) and short (8 h) time course experiments, the IGF-I/IGFl gene expression profiles following T3 treatment in the tissue cultures of both species exhibited closely similar pattern and trend. Moreover, exposure of zebrafish and amphioxus to T3in vivo for 72 h induced a significant increase in the expression of IGF-I/IGFl genes in both the liver and the hepatic caecum. These data together suggest that amphioxus and zebrafish both share a similar regulatory mechanism of IGF gene expression in response to T3, providing an evidence for the presence of a vertebrate-like TH/IGF signaling pathway in the protochordate amphioxus.