Previous studies have demonstrated the transcriptional repressive property of the atypical nuclear receptor, small heterodimer partner (SHP), on NeuroD. NeuroD is a basic helix-loop-helix transcription factor that has also been shown to be important in modulating secretin gene expression. The present study revealed the activation of the human secretin core promotor by overexpressing NeuroD, and the localization of SHP and secretin-producing cells in mouse duodenal epithelium by immunohistochemical stainings. These results indicated that SHP and secretin are potentially co-expressed and lead us to propose a novel regulatory pathway, in which SHP represses NeuroD's positive regulatory activity on secretin gene.