Transcriptional regulation of 5′-flanking regions of stanniocalcin genes by estrogen receptor and estrogen receptor-related receptor

Stanniocalcin (STC), a glycoprotein hormone originally identified in bony fish, is a regulator of calcium and phosphate homeostasis. Two related STC genes, STC1 and STC2, are expressed in various tissues in vertebrates, but their transcriptional regulation and differences between the two genes are poorly understood. The aim of this study was to determine and compare estrogen-dependent transcriptional activities of the 5′-flanking regions of the mouse STC1 (mStc1) and STC2 (mStc2) genes. Using HEK293 cells and a transient transfection method, the transcriptional activity of the mStc1 and mStc2 genes was measured by a luciferase reporter assay. In this study, we have identified the existence of putative estrogen response elements (EREs) and estrogen receptor (ER)-related receptor (ERR) response elements (ERREs) in the 5′-flanking regions of the mStc1 gene, but the putative ERRE sites only within the mStc2. Luciferase reporter assays showed that ligand bound ERα and ERRγ increase the transcription of mStc1 but not mStc2. In addition, the ERα- and ERRγ-mediated transactivation of the 5′-flanking region of mStc1 was further enhanced by the coregulators, steroid receptor coactivator 1 and peroxisome proliferator-activated receptor γ coactivator 1 α. Taken together, our results suggest that the putative promoter region of mStc1, but not mStc2, is transcriptionally enhanced by ligand-activated ERα and ERRγ.