Mechanism of action of 1-25-dihydroxy-vitamin D3 (1,25(OH)2D3). 1,25(OH)2D3 is transported to the target cell bound to the vitamin D-binding protein (VDBP). The free form of 1,25(OH)2D3 enters the target cell and interacts with the vitamin D receptor (VDR) at the nucleus. This complex is phosphorylated and combined with the nuclear accessory factor (RAF). This forms a heterodimer, which then interacts with the vitamin D responsive element (VDRE). The VDRE then either promotes or inhibits the transcription of messenger RNA (mRNA) for proteins regulated by 1,25(OH)2D3, such as Ca-binding proteins, the 25-hydroxy-vita-min D3 24-hydroxylase enzyme, and parathyroid hormone. Pi—inorganic phosphate. (Adapted from Holick [8].)

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