Vitamin D and barrier function: a novel role for extra-renal 1 alpha-hydroxylase

Mol Cell Endocrinol. 2004 Feb 27;215(1-2):31-8. doi: 10.1016/j.mce.2003.11.017.


Much recent attention has focused on the positive health benefits of vitamin D beyond its established role in calcium homeostasis. Epidemiology has highlighted the link between vitamin D deficiency and prevalent diseases such as common cancers and autoimmune disease. Furthermore, studies in vitro have shown that the active form of vitamin D, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) is a potent antiproliferative and immunosuppressive agent. The net effect of this has been the generation and analysis of synthetic analogues of vitamin D for potential use in the treatment of cancers and other disorders including psoriasis. However, there is increasing interest in the impact that vitamin D may have on normal physiology above and beyond its classical effects on calcium homeostasis and bone metabolism. We have postulated that these 'non-calcemic' effects of vitamin D are dependent on extra-renal synthesis of 1,25(OH)(2)D(3) via the enzyme 1 alpha-hydroxylase at barrier sites throughout the body. Here we present a review of the mechanisms associated with extra-renal 1 alpha-hydroxylase, and we also speculate on how this 'new' physiological role for vitamin D may actually reflect an ancient function for this pluripotent secosteroid.

Publication types

  • Review

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / genetics
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / metabolism*
  • Animals
  • Calcitriol / metabolism*
  • Humans
  • Kidney / enzymology
  • Vitamin D / metabolism*


  • Vitamin D
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
  • Calcitriol