Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2009 Jan;94(1):26-34.
doi: 10.1210/jc.2008-1454. Epub 2008 Oct 14.

Nonclassic actions of vitamin D

Daniel Bikle  1
Affiliations
Review

Nonclassic actions of vitamin D

Daniel Bikle. J Clin Endocrinol Metab. 2009 Jan.

Abstract

Context: Vitamin D receptors are found in most tissues, not just those participating in the classic actions of vitamin D such as bone, gut, and kidney. These nonclassic tissues are therefore potential targets for the active metabolite of vitamin D, 1,25(OH)(2)D. Furthermore, many of these tissues also contain the enzyme CYP27B1 capable of producing 1,25(OH)(2)D from the circulating form of vitamin D. This review was intended to highlight the actions of 1,25(OH)(2)D in several of these tissues but starts with a review of vitamin D production, metabolism, and molecular mechanism.

Evidence acquisition: Medline was searched for articles describing actions of 1,25(OH)(2)D on parathyroid hormone and insulin secretion, immune responses, keratinocytes, and cancer.

Evidence synthesis: Vitamin D production in the skin provides an efficient source of vitamin D. Subsequent metabolism to 1,25(OH)(2)D within nonrenal tissues differs from that in the kidney. Although vitamin D receptor mediates the actions of 1,25(OH)(2)D, regulation of transcriptional activity is cell specific. 1,25(OH)(2)D inhibits PTH secretion but promotes insulin secretion, inhibits adaptive immunity but promotes innate immunity, and inhibits cell proliferation but stimulates their differentiation.

Conclusions: The nonclassic actions of vitamin D are cell specific and provide a number of potential new clinical applications for 1,25(OH)(2)D(3) and its analogs. However, the use of vitamin D metabolites and analogs for these applications remains limited by the classic actions of vitamin D leading to hypercalcemia and hypercalcuria.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Production of vitamin D2 and vitamin D3. Ergosterol in plants and 7-dehydrocholesterol in skin are the precursors for vitamin D2 and vitamin D3, respectively. UV light B breaks the B chain of each molecule to form the pre-D isomer, which then undergoes isomerization to D. D2 and D3 differ only in the side chain in which D2 has a double bond between C22–C23 and a methyl group at C24. These differences alter somewhat its binding to DBP and metabolism.
Figure 2
Figure 2
Regulation of 1,25(OH)2D production in the kidney. PTH stimulates and FGF23 inhibits 1,25(OH)2D production in the kidney. In turn 1,25(OH)2D inhibits PTH production and secretion from the parathyroid glands and stimulates FGF23 production from bone.
Figure 3
Figure 3
Regulation of immune function by 1,25(OH)2D. 1,25(OH)2D suppresses adaptive immunity (A) by inhibiting the maturation of dendritic cells, reducing their capacity to present antigen to CD4 cells. 1,25(OH)2D further inhibits the proliferation and differentiation of CD4 cells into Th1 and Th17 cells and promotes the production of Th2 and Treg cells. On the other hand 1,25(OH)2D promotes innate immunity (B) in that when the macrophage is activated by TLRs, VDR and CYP27B1 are induced enabling the macrophage to produce 1,25(OH)2D, which then induces cathelicidin, a potent antimicrobial peptide.
See this image and copyright information in PMC

References

    1. Armas LA, Hollis BW, Heaney RP 2004 Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab 89:5387–5391 - PubMed
    1. Romagnoli E, Mascia ML, Cipriani C, Fassino V, Mazzei F, D'Erasmo E, Carnevale V, Scillitani A, Minisola S 2008 Short and long-term variations in serum calciotropic hormones after a single very large dose of ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) in the elderly. J Clin Endocrinol Metab 93:3015–3020 - PubMed
    1. Holick MF, Biancuzzo RM, Chen TC, Klein EK, Young A, Bibuld D, Reitz R, Salameh W, Ameri A, Tannenbaum AD 2008 Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D. J Clin Endocrinol Metab 93:677–681 - PMC - PubMed
    1. Holick MF, MacLaughlin JA, Clark MB, Holick SA, Potts Jr JT, Anderson RR, Blank IH, Parrish JA, Elias P 1980 Photosynthesis of previtamin D3 in human skin and the physiologic consequences. Science 210:203–205 - PubMed
    1. Holick MF, MacLaughlin JA, Doppelt SH 1981 Regulation of cutaneous previtamin D3 photosynthesis in man: skin pigment is not an essential regulator. Science 211:590–593 - PubMed

Publication types