Vitamin D receptor (VDR)-mediated actions of 1α,25(OH)                          2                         vitamin D                         3: Genomic and non-genomic mechanisms

Mark R. Haussler; Peter W. Jurutka; Mathew Mizwicki; Anthony W. Norman

doi:10.1016/j.beem.2011.05.010

Vitamin D receptor (VDR)-mediated actions of 1α,25(OH) ₂ vitamin D ₃: Genomic and non-genomic mechanisms

Mark R. Haussler, Peter W. Jurutka, Mathew Mizwicki, Anthony W. Norman

Research output: Contribution to journal › Review article › peer-review

554 Scopus citations

Abstract

The conformationally flexible secosteroid, 1α,25(OH) ₂ vitamin D ₃ (1α,25(OH) ₂ D ₃ ) initiates biological responses via binding to the vitamin D receptor (VDR). The VDR contains two overlapping ligand binding sites, a genomic pocket (VDR-GP) and an alternative pocket (VDR-AP), that respectively bind a bowl-like ligand configuration (gene transcription) or a planar-like ligand shape (rapid responses). When occupied by 1α,25(OH) ₂ D ₃ , the VDR-GP interacts with the retinoid X receptor to form a heterodimer that binds to vitamin D responsive elements in the region of genes directly controlled by 1α,25(OH) ₂ D ₃ . By recruiting complexes of either coactivators or corepressors, activated VDR modulates the transcription of genes encoding proteins that promulgate the traditional genomic functions of vitamin D, including signaling intestinal calcium and phosphate absorption to effect skeletal and calcium homeostasis. 1α,25(OH) ₂ D ₃ /VDR control of gene expression and rapid responses also delays chronic diseases of aging such as osteoporosis, cancer, type-1 and -2 diabetes, arteriosclerosis, vascular disease, and infection.

Original language	English (US)
Pages (from-to)	543-559
Number of pages	17
Journal	Best Practice and Research: Clinical Endocrinology and Metabolism
Volume	25
Issue number	4
DOIs	https://doi.org/10.1016/j.beem.2011.05.010
State	Published - Aug 2011
Externally published	Yes

Keywords

coactivator
corepressor
genomic responses
ligand conformation
rapid responses
retinoid X receptor
transcription
vitamin D receptor
vitamin D responsive elements

ASJC Scopus subject areas

Endocrinology, Diabetes and Metabolism
Endocrinology

Access to Document

10.1016/j.beem.2011.05.010

Cite this

Haussler, M. R., Jurutka, P. W., Mizwicki, M., & Norman, A. W. (2011). Vitamin D receptor (VDR)-mediated actions of 1α,25(OH) ₂ vitamin D ₃: Genomic and non-genomic mechanisms. Best Practice and Research: Clinical Endocrinology and Metabolism, 25(4), 543-559. https://doi.org/10.1016/j.beem.2011.05.010

Vitamin D receptor (VDR)-mediated actions of 1α,25(OH) ₂ vitamin D ₃: Genomic and non-genomic mechanisms. / Haussler, Mark R.; Jurutka, Peter W.; Mizwicki, Mathew et al.
In: Best Practice and Research: Clinical Endocrinology and Metabolism, Vol. 25, No. 4, 08.2011, p. 543-559.

Research output: Contribution to journal › Review article › peer-review

Haussler, MR, Jurutka, PW, Mizwicki, M & Norman, AW 2011, 'Vitamin D receptor (VDR)-mediated actions of 1α,25(OH) ₂ vitamin D ₃: Genomic and non-genomic mechanisms', Best Practice and Research: Clinical Endocrinology and Metabolism, vol. 25, no. 4, pp. 543-559. https://doi.org/10.1016/j.beem.2011.05.010

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abstract = " The conformationally flexible secosteroid, 1α,25(OH) 2 vitamin D 3 (1α,25(OH) 2 D 3 ) initiates biological responses via binding to the vitamin D receptor (VDR). The VDR contains two overlapping ligand binding sites, a genomic pocket (VDR-GP) and an alternative pocket (VDR-AP), that respectively bind a bowl-like ligand configuration (gene transcription) or a planar-like ligand shape (rapid responses). When occupied by 1α,25(OH) 2 D 3 , the VDR-GP interacts with the retinoid X receptor to form a heterodimer that binds to vitamin D responsive elements in the region of genes directly controlled by 1α,25(OH) 2 D 3 . By recruiting complexes of either coactivators or corepressors, activated VDR modulates the transcription of genes encoding proteins that promulgate the traditional genomic functions of vitamin D, including signaling intestinal calcium and phosphate absorption to effect skeletal and calcium homeostasis. 1α,25(OH) 2 D 3 /VDR control of gene expression and rapid responses also delays chronic diseases of aging such as osteoporosis, cancer, type-1 and -2 diabetes, arteriosclerosis, vascular disease, and infection.",

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