Vitamin D and barrier function: a novel role for extra-renal 1 alpha-hydroxylase.
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.
Hewison
Martin
M
Division of Medical Sciences, Institute of Clinical Research, The University of Birmingham, Queen Elizabeth Hospital, Birmingham B15 2TH, UK. m.hewison@bham.ac.uk
Zehnder
Daniel
D
Chakraverty
Ronjon
R
Adams
John S
JS
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002117:Calcitriol / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000201:enzymology; D014807:Vitamin D / Q000378:metabolism*
D014807:Vitamin D; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002117:Calcitriol