Ann Pediatr Endocrinol Metab.  2013 Jun;18(2):45-54. 10.6065/apem.2013.18.2.45.

The pleiomorphic actions of vitamin D and its importance for children

• Kim SY

• KMID: 2047460
• DOI: http://doi.org/10.6065/apem.2013.18.2.45

Abstract

Knowledge regarding the physiological role and dietary requirements of vitamin D has dramatically expanded over the past several decades. The "new" vitamin D is not only a mediator of calcium homeostasis, it also has important immunomodulatory, antimicrobial, and antiproliferative actions. In spite of the interest in vitamin D as a mediator in many chronic diseases of adulthood such as cancer and type II diabetes, less attention has been given to the implications of the new understanding of vitamin D for child and adolescent health. Recently, rickets caused by vitamin D deficiency is resurging in developed countries. Therefore, pharmacokinetic studies and epidemiologic research that incorporates clinical and functional outcomes are needed to clarify the role of vitamin D in growth and development in Korean children and adolescents and to determine vitamin D dietary requirements.

Keyword

Vitamin D; Vitamin D receptor; Child; Growth

MeSH Terms

Adolescent
Calcium
Child
Chronic Disease
Developed Countries
Growth and Development
Homeostasis
Humans
Nutritional Requirements
Receptors, Calcitriol
Rickets
Vitamin D
Vitamin D Deficiency
Vitamins
Calcium
Receptors, Calcitriol
Vitamin D
Vitamins

Figure

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  Fig. 1 (A) Production of vitamin D from the skin via ultraviolet (290-330 nm) in a nonenzymatic manner. (B) The synthesis of vitamin D metabolites including the inactive form, 24,25-dihydroxyvitamin D, and the active form, 1,25-dihydroxyvitamin D (1,25(OH)2D). The process in controlled at several levels, including the liver, kidney, and peripheral tissues, and is regulated by systemic hormones including parathyroid hormone (PTH), 1,25(OH)2D, and fibroblast gowth factor 23 (FGF23). Calcium and phosphorus are also major modulators of 1-αhydroxylase and 24,25-hydroxylase activity through their effects on PTH and FGF23. 25(OH)D3, 25-hydroxyvitamin D3. Adapted from PubChem, National Center for Biotechnology Information, U.S. National Library of Medicine (www.ncbi.nlm.nih.gov/pccompound).

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  Fig. 2 Vitamin D metabolism are shown. UV, ultraviolet; DBP, vitamin D-binding protein; PTH, parathyroid hormone; FGF23, fibroblast growth factor 23; 1,25(OH)2D3, 1,25-dihydroxyvitamin D3.

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  Fig. 3 Vitamin D receptor. The N-terminal region is short that, this region is followed by two zinc fingers, which constitute the principal DNA-binding domain. Nuclear localizing signals (NLS) are found within and just C-terminal to the DNA-binding domain. The ligand-binding domain (LBD) makes up the bulk of the C-terminal half of the molecule, with the AF2 domain occupying the most C-terminal region. The AF2 domain is largely responsible for binding to coactivators such as the steroid receptor coactivator family and vitamin D receptor-interacting protein complex. in the presence of ligand. Regions on the second zinc finger and within the LBD facilitate heterodimerization with retinoid X receptor (RXR).

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  Fig. 4 The diagram of classic vitamin D signaling pathway. Vitamin D binds to its receptor, which dimerizes, preferentially vitamin D response elements in the DNA to regulate transcriprion. VDR, vitamin D receptor; RXR, retinoid X receptor.

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  Fig. 5 Effects of vitamin D on the human innate (upper) and adaptive immune response (lower). When activated by mitogen or specific antigen, macrophages, dendritic cells, and lymphocytes express the vitamin D receptor (VDR), thereby becoming targets for the active vitamin D metabolite, 1,25-dihydroxyvitamin D (1,25(OH)2D). Macrophages and dendritic cells can also express the CYP27B1-hydroxylase that synthesizes 1,25(OH)2D from substrate 25(OH)D, the major circulating metabolite of vitamin D and acknowledged best indicator of the amount of vitamin D entering the host via cutaneous synthesis or that ingested in the diet. Operating in an intracrine mode, 1,25(OH)2D promotes microbial killing in the macrophage, whereas it inhibits maturation and the antigen-presenting capacity of the dendritic cell. If 1,25(OH)2D escapes the confines of the macrophage or dendritic cell in sufficient amount, it can act on VDR-expressing lymphocytes recruited to the local inflammatory microenvironment. The major bioaction of 1,25(OH)2D acting through the VDR in lymphocytes is to inhibit their proliferation and differentiation to maturity; this antiproliferative effect is more profound on the classes of helper than suppressor cells, leading to generalized suppression of the adaptive immune response.

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