Direct suppression of Pth gene expression by the vitamin D prohormones doxercalciferol and calcidiol requires the vitamin D receptor.

Article Details

Citation

Copy to clipboard

Ritter CS, Brown AJ

Direct suppression of Pth gene expression by the vitamin D prohormones doxercalciferol and calcidiol requires the vitamin D receptor.

J Mol Endocrinol. 2011 Feb 15;46(2):63-6. doi: 10.1677/JME-10-0128. Print 2011 Apr.

PubMed ID

21169421 [ View in PubMed

]

Abstract

Vitamin D compounds regulate PTH at the transcriptional level, presumably via binding to the vitamin D receptor (VDR), but the exact mechanism is presently unclear. We recently reported that the several vitamin D prohormones with low VDR affinity suppressed PTH, even when their activation was inhibited, raising the possibility that their actions may be VDR independent. To test this hypothesis, we developed a novel organ culture that allowed the assessment of activities of the prohormones on PTH release from wild-type and VDR-null thyroparathyroid explants. The cultures remained viable with respect to PTH release for at least 2 weeks. Full suppression of PTH by the native vitamin D hormone, 1alpha,25-dihydroxyvitamin D(3) [1alpha,25 (OH)(2)D(3)], required 2 days, consistent with a transcriptional mechanism, and was reversible, indicating that reduced PTH was not attributable to cell death. Inhibition of PTH release by 1alpha,25 (OH)(2)D(3) and two prohormones, 25-hydroxyvitamin D(3) and 1alpha-hydroxyvitamin D(2), was observed in explants from wild-type mice but not in those from VDR-null mice. These findings 1) are the first direct demonstration of the role of the VDR in regulation of PTH by 1alpha,25(OH)(2)D(3), 2) confirm that the suppressive actions of the vitamin D prohormones are mediated by the VDR, and 3) introduce a novel organ culture model that allows the ex vivo study of the function of parathyroid glands from transgenic animals.

DrugBank Data that Cites this Article

Drugs

Doxercalciferol

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Doxercalciferol	Vitamin D3 receptor	Protein	Humans	Unknown	Suppressor	Details