The role of Vitamin D3 metabolism in prostate cancer

J Steroid Biochem Mol Biol. 2004 Nov;92(4):317-25. doi: 10.1016/j.jsbmb.2004.10.007. Epub 2004 Dec 19.

Abstract

Vitamin D deficiency increases risk of prostate cancer. According to our recent results, the key Vitamin D hormone involved in the regulation of cell proliferation in prostate is 25(OH) Vitamin D3. It is mainly acting directly through the Vitamin D receptor (VDR), but partially also through its 1alpha-hydroxylation in the prostate. A deficiency of 25(OH) Vitamin D is common especially during the winter season in the Northern and Southern latitudes due to an insufficient sun exposure, but Vitamin D deficient diet may partially contribute to it. A lack of Vitamin D action may also be due to an altered metabolism or Vitamin D resistance. Vitamin D resistance might be brought up by several mechanisms: Firstly, an increased 24-hydroxylation may increase the inactivation of hormonal Vitamin D metabolites resulting in a Vitamin D resistance. This is obvious in the cancers in which an oncogenic amplification of 24-hydroxykase gene takes place, although an amplification of this gene in prostate cancer has not yet been described. During the aging, the activity of 24-hydroxylase increases, whereas 1alpha-hydroxylation decreases. Furthermore, it is possible that a high serum concentration of 25(OH)D3 could induce 24-hydroxylase expression in prostate. Secondly, Vitamin D receptor gene polymorphism or defects may result in a partial or complete Vitamin D resistance. Thirdly, an overexpression or hyperphosphorylation of retinoblastoma protein may result in an inefficient mitotic control by Vitamin D. Fourthly, endogenous steroids (reviewed by [D.M. Peehl, D. Feldman, Interaction of nuclear receptor ligands with the Vitamin D signaling pathway in prostate cancer, J. Steroid Biochem. Mol. Biol. (2004)]) and phytoestrogens may modulate the expression of Vitamin D metabolizing enzymes. In summary, the local metabolism of hormonal Vitamin D seems to play an important role in the development and progression of prostate cancer.

Publication types

  • Review

MeSH terms

  • 24,25-Dihydroxyvitamin D 3 / blood
  • 24,25-Dihydroxyvitamin D 3 / metabolism
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / genetics
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / metabolism
  • Calcifediol / blood
  • Calcifediol / deficiency
  • Calcifediol / physiology
  • Calcitriol / pharmacology
  • Calcitriol / physiology
  • Cell Proliferation / drug effects
  • Cholecalciferol / metabolism*
  • Cytochrome P-450 Enzyme Inhibitors
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Phytoestrogens / pharmacology
  • Prostate / drug effects
  • Prostate / metabolism
  • Prostate / pathology
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Receptors, Calcitriol / genetics
  • Receptors, Calcitriol / metabolism
  • Steroid Hydroxylases / antagonists & inhibitors
  • Steroid Hydroxylases / genetics
  • Steroid Hydroxylases / metabolism
  • Vitamin D3 24-Hydroxylase

Substances

  • Cytochrome P-450 Enzyme Inhibitors
  • Phytoestrogens
  • Receptors, Calcitriol
  • Cholecalciferol
  • 24,25-Dihydroxyvitamin D 3
  • Cytochrome P-450 Enzyme System
  • Steroid Hydroxylases
  • Vitamin D3 24-Hydroxylase
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
  • Calcitriol
  • Calcifediol