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Vitamin D Receptors can be activated by other than Vitamin D - March 2015

[Current Topics on Vitamin D. Nonsecosteroidal vitamin D modulators and prospects for their thepapeutic application].

[Article in Japanese]
Clin Calcium. 2015 Mar;25(3):403-11. doi: CliCa.
Makishima M1.
1Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, Japan.

Vitamin D is a secosteroid, in which the B ring of the steroid structure is ruptured. The active form of vitamin D, 1α, 25-dihydroxyvitamin D3 [1,25 (OH) 2D3], regulates numerous physiological and pharmacological processes, including bone and calcium homeostasis, cellular growth and differentiation, immunity, and cardiovascular function, through binding to the vitamin D receptor (VDR), a member of the nuclear receptor superfamily. VDR ligands are promising in the treatment of bone and mineral disorders, cancer, autoimmune disease, and cardiovascular disease. However, the calcemic effect of vitamin D derivatives has limited their clinical application.

Recently, nonsecosteroidal VDR modulators (VDRMs) have been developed. Several VDRMs have better therapeutic efficacy when compared to 1,25 (OH) 2D3 in experimental models of cancer and osteoporosis with less induction of hypercalcemia. Analysis of crystal structures reveals that nonsecosteroidal VDRMs bind to VDR in a position similar to 1,25 (OH) 2D3 and that hydrogen bond interactions between ligands and VDR are important for VDR transactivation. Pharmacokinetics of nonsecosteroidal VDRMs may be related to their less calcemic effect. Nonsecosteroidal VDRMs can induce VDR conformation distinct from that by 1,25 (OH) 2D3, likely leading to selective gene expression. Although the potential risk of unexpected adverse effects needs be considered, further development of nonsecosteroidal VDRMs should expand the possibility of VDR-targeted approaches.

PMID: 25716814

This is one article in special March 2015 issue – which included the following

Action through the nuclear receptor of vitamin D and the mechanism of action
Vitamin D endocrine system and the PTH · FGF23 signal cross-talk
Animal evolution and vitamin D
Effects on immune cells of vitamin D and the infection defense
Vitamin application to action and treatment of D to the skin cells
Vitamin anti-tumor effect of D
Vitamin influence the working of D to the muscle cells to motor function
Protein interactions of the active form of vitamin D and the onset of action
The action in bone remodeling control system of-active form of vitamin D
Non-secosteroids vitamin D receptor agonist and prospects to its therapeutic applications
Vitamin D and chronic kidney disease (CKD-MBD)
Erude Cal affect on osteoporosis treatment and renal function by Thor
Combination therapy of bone resorption inhibitor and the active form of vitamin D
Active form of vitamin D 3 for the impact on renal function due to preparation

See also VitaminDWiki