Involvement of GCMB in the transcriptional regulation of the human parathyroid hormone gene in a parathyroid-derived cell line PT-r: effects of calcium and 1,25(OH)2D3.

Abstract

Expression of the PTH gene is known to be under strict tissue-specific control and is also regulated by extracellular calcium and 1,25(OH)(2)D. However, the precise mode of transcriptional regulation remains to be elucidated, because of the unavailability of appropriate cell lines derived from the parathyroid gland. We tried to identify the transcription factor(s) regulating the human PTH gene transcription using the PT-r cell line. We found that PT-r cells endogenously express PTH and several parathyroid-related genes. Using the cells, we investigated the transcriptional regulation of human PTH gene. We found that GCMB binds to the PTH gene 5'-promoter (-390/-383 bp) and positively regulates its transcription. On the other hand, 1,25(OH)(2)D(3), and, in the presence of the calcium sensing receptor, high extracellular calcium, exerted inhibitory effects on PTH gene expression. These results indicate that GCMB and vitamin D receptor are involved in the positive and negative regulation of PTH gene expression, respectively. Our data also suggest that PT-r cells retain some of the characteristics of parathyroid cells.