In conclusion, we provide data supporting alternative mechanisms for extrahepatic regulatory mechanisms of SEPP1 expression that may help explain SEPP1 expression in inflammation, development and differentiation. We took advantage of an engineered, fusion transcription factor that contains the GR’s DNA binding domain coupled with a strong transactivation domain, along with RXR, to identify the site responsible for the induction of SEPP1 expression. However, our studies revealed that the native GR inhibits the expression of SEPP1 through an indirect mechanism. Therefore, the ability of corticosteroids, and perhaps retinoids, to modulate SEPP1 expression may be a mechanism that could result in altered tissue selenium distribution since SelP is the major carrier of selenium.
