Evidence for 1,25-Dihydroxyvitamin D3-Independent Transactivation by the Vitamin D Receptor

February 2007 in “ Journal of biological chemistry/The Journal of biological chemistry ”

Tara I. Ellison, Richard L. Eckert, Paul N. MacDonald

Vitamin D Receptor VDR 1,25-Dihydroxyvitamin D3 1,25(OH)2D3 keratinocytes 24-hydroxylase promoter phosphorylation VDR-RXR heterodimerization psoriasis skin cancer hypercalcemia Vitamin D3

Studysummary This study found that vitamin D receptor activation in primary keratinocytes can occur independently of the 1,25-dihydroxyvitamin D<sub>3</sub> ligand, likely through interaction with retinoid X receptors.

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The study provided evidence that the Vitamin D Receptor (VDR) could activate transcription independently of its ligand, 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3), specifically in primary keratinocytes. This was demonstrated by the activation of the 24-hydroxylase promoter without 1,25(OH)2D3. The findings suggested that VDR might interact with other ligands or undergo modifications such as phosphorylation to exert its effects. This ligand-independent activity was unique to keratinocytes and selective for certain promoters, indicating a potential for targeted therapeutic strategies in skin disorders like psoriasis and skin cancer without causing hypercalcemia. The study also highlighted the importance of VDR-RXR heterodimerization in this process.

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research Targeting Expression of the Human Vitamin D Receptor to the Keratinocytes of Vitamin D Receptor Null Mice Prevents Alopecia

115 citations , December 2001 in “Endocrinology”

This study found that restoring vitamin D receptor expression specifically in the keratinocytes of VDR null mice prevented alopecia and enhanced hair follicle response during anagen initiation.

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137 citations , April 2001 in “Journal of Clinical Investigation”

This study found that alopecia in VDR-null mice persists despite undetectable vitamin D levels, indicating a defect in epithelial-mesenchymal communication due to the absence of ligand-independent receptor function.

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519 citations , October 1998 in “Endocrinology”

The study found that normalizing mineral ion levels in vitamin D receptor-ablated mice prevented hyperparathyroidism and bone disorders but did not address hair loss, indicating the VDR's role in hair growth.