Extra-renal 25-hydroxyvitamin D3-1alpha-hydroxylase in human health and disease

J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):316-21. doi: 10.1016/j.jsbmb.2006.12.078.

Abstract

Although ectopic expression of 25-hydroxyvitamin D(3)-1alpha-hydroxylase (1alpha-OHase) has been recognized for many years, the precise function of this enzyme outside the kidney remains open to debate. Three specific aspects of extra-renal 1alpha-OHase have attracted most attention: (i) expression and regulation in non-classical tissues during normal physiology; (ii) effects on the immune system and inflammatory disease; (iii) expression and function in tumors. The most well-recognized manifestation of extra-renal 1alpha-OHase activity remains that found in some patients with granulomatous diseases where locally synthesized 1alpha,25(OH)(2)D(3) has the potential to spill-over into the general circulation. However, immunohistochemistry and mRNA analyses suggest that 1alpha-OHase is also expressed by a variety of normal human tissues including the gastrointestinal tract, skin, vasculature and placenta. This has promoted the idea that autocrine/paracrine synthesis of 1,25(OH)(2)D(3) contributes to normal physiology, particularly in mediating the potent effects of vitamin D on innate (macrophage) and acquired (dendritic cell) immunity. We have assessed the capacity for synthesis of 1,25(OH)(2)D(3) in these cells and the functional significance of autocrine responses to 1alpha-hydroxylase. Data suggest that local synthesis of 1,25(OH)(2)D(3) may be a preferred mode of response to antigenic challenge in many tissues.

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / metabolism*
  • Calcifediol / biosynthesis
  • Cells, Cultured
  • Dendritic Cells / enzymology
  • Disease
  • Health*
  • Humans
  • Kidney / enzymology*

Substances

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
  • Calcifediol