Vitamin D and DBP

The free hormone hypothesis revisited

Rene F. Chun, Bradford E. Peercy, Eric Orwoll, Carrie Nielson, John S. Adams, Martin Hewison

Research output: Contribution to journalArticle

174 Citations (Scopus)

Abstract

The last five years have witnessed a remarkable renaissance in vitamin D research and a complete re-evaluation of its benefits to human health. Two key factors have catalyzed these changes. First, it now seems likely that localized, tissue-specific, conversion of 25-hydroxyvitamin D (25OHD) to 1,25-dihydroxyvitamin D (1,25(OH)2D) drives many of the newly recognized effects of vitamin D on human health. The second key factor concerns the ongoing discussion as to what constitutes adequate or optimal serum vitamin D (25OHD) status, with the possibility that vitamin D-deficiency is common to communities across the globe. These two concepts appear to be directly linked when low serum concentrations of 25OHD compromise intracrine generation of 1,25(OH)2D within target tissues. But, is this an over-simplification? Pro-hormone 25OHD is a lipophilic molecule that is transported in the circulation bound primarily to vitamin D binding protein (DBP). While the association between 25OHD and DBP is pivotal for renal handling of 25OHD and endocrine synthesis of 1,25(OH)2D, what is the role of DBP for extra-renal synthesis of 1,25(OH)2D? We hypothesize that binding to DBP impairs delivery of 25OHD to the vitamin D-activating enzyme 1α-hydroxylase in some target cells. Specifically, it is unbound, 'free' 25OHD that drives many of the non-classical actions of vitamin D. Levels of 'free' 25OHD are dependent on the concentration of DBP and alternative serum binding proteins such as albumin, but will also be influenced by variations in DBP binding affinity for specific vitamin D metabolites. The aim of this review will be to discuss the merits of 'free 25OHD' as an alternative marker of vitamin D status, particularly in the context of non-classical responses to vitamin D. This article is part of a Special Issue entitled '16th Vitamin D Workshop'.

Original languageEnglish (US)
Pages (from-to)132-137
Number of pages6
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume144
Issue numberPART A
DOIs
StatePublished - 2014

Fingerprint

Vitamin D
Carrier Proteins
Hormones
4 alpha-glucanotransferase
Vitamin D-Binding Protein
Kidney
Health
Tissue
Vitamin D Deficiency
Mixed Function Oxygenases
Serum
Protein Binding
Metabolites
Blood Proteins
Albumins
Education
Association reactions
Molecules
Research
Enzymes

Keywords

  • Bioavailable
  • Free hormone
  • Intracrine
  • Megalin
  • Vitamin D
  • Vitamin D binding protein

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Cell Biology
  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism
  • Molecular Medicine

Cite this

Vitamin D and DBP : The free hormone hypothesis revisited. / Chun, Rene F.; Peercy, Bradford E.; Orwoll, Eric; Nielson, Carrie; Adams, John S.; Hewison, Martin.

In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 144, No. PART A, 2014, p. 132-137.

Research output: Contribution to journalArticle

Chun, Rene F. ; Peercy, Bradford E. ; Orwoll, Eric ; Nielson, Carrie ; Adams, John S. ; Hewison, Martin. / Vitamin D and DBP : The free hormone hypothesis revisited. In: Journal of Steroid Biochemistry and Molecular Biology. 2014 ; Vol. 144, No. PART A. pp. 132-137.
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