PTH Gene Transcription
Calcium and calcitriol negatively regulate transcription of the pre-pro-PTH gene through distinct upstream response elements. The calcium response element (CaRE) is located approximately 3.5 kilobases upstream from the pre-pro-PTH gene.1 G protein-coupled signaling via the CaSR leads to changes in intracellular Ca2+. It remains unclear whether the actual steady-state cytosolic Ca2+ concentration, the rate of change in cytosolic Ca2+, or variations in the frequency and amplitude of oscillations in cytosolic Ca2+ are responsible for regulating pre-pro-PTH gene transcription.
The vitamin D response element (VDRE) is located approximately 101 to 125 base pairs upstream of the transcriptional start site.2 The regulation of mRNA transcription depends on calcitriol binding to VDR, a nuclear hormone receptor, and subsequent formation of a complex with RXR. Binding of the VDR-RXR complex to VDRE controls the rate of PTH gene transcription through RNA polymerase II inhibition.