تسجيل الدخول

تسجيل

1α,25(OH)2D3+VDR Mediated Genomic and Nongenomic Biological Responses

المؤلف:  Norman, A. W., & Henry, H. L.

المصدر:  Hormones

الجزء والصفحة:  3rd edition , p207-208

2026-07-30

74

The binding of 1α,25(OH)2D3 to the VDR in the cell nucleus initiates a series of events that ultimately can result in changes in the selective transcription of ~3% of the human genome of ~20,000 genes (i.e., ~600 genes). The overall process of regulating gene transcription is complex and can result in either stimulation or repression of gene transcription. Extensive detail of the VDR structure has emerged as a consequence of X-ray crystallographic as well as mutagenesis studies. The liganded VDR interacts with the unliganded retinoid-X receptor (RXR) to form a heterodimer (VDR-RXR). The heterodimer then recruits either coactivator or corepressor proteins and other transcription factors so as to be able to recognize and interact specifically with vitamin D response elements in the promoter of the selected gene to either upregulate or downregulate its transcription into mRNA.

Besides the VDR mediated genomic effects, there are many examples of 1α,25(OH)2D3 mediated rapid responses that can occur in minutes to under 1 hour. These are known to occur in osteoblasts, intestinal cells, endothelial cells, Sertoli cells, human spermatazoa, and pancreatic β-cells. Comparable rapid responses are known for all other steroid hormone receptors. The cellular site of initiation of rapid responses is the 1α,25(OH)2D3 liganded VDR in the caveolae-containing plasma membrane. Depending upon the cell type and circumstances, a wide variety of second messengers are known to be stimulated by the VDR-1α,25(OH)2D3; these include opening of chloride or calcium channels, stimulation of exocytosis, and activation of second-messenger signaling pathways (e.g., activation of protein kinase C or phosphoinositide turnover).