Hormone-nuclear receptor interactions in health and disease. Vitamin D resistance.
Tissue resistance to vitamin D, or vitamin D-dependent rickets (VDDR), can be classified as two separate conditions--VDDR type I and VDDR type II--both of which present with the classical clinical, radiological and biochemical features of rickets despite adequate vitamin D intake. VDDR II can also be associated with alopecia, for reasons that are not clear. The two syndromes result from distinct disorders of vitamin D metabolism or action. Both are inherited in an autosomal recessive fashion. VDDR I is caused by decreased production of the active form of vitamin D, 1,25-dihydroxycholecalciferol, with the proposed defect being in the gene encoding the enzyme 1 alpha-hydroxylase. VDDR II results from mutations in the gene for the intracellular receptor for 1,25-dihydroxycholecalciferol (vitamin D receptor), resulting in changes in hormone or DNA binding, depending on the mutation. These mutations are analogous to those affecting receptors for other steroid-thyroid hormones, which have also been shown to cause resistance to hormone action.
Hewison
M
M
Department of Medicine, University College London Medical School, Middlesex Hospital, UK.
O'Riordan
J L
JL
D004351:Drug Resistance; D006801:Humans; D007015:Hypophosphatemia, Familial / Q000145:classification / Q000503:physiopathology; D008659:Metabolic Diseases / Q000503:physiopathology; D018167:Receptors, Calcitriol / Q000235:genetics; D014807:Vitamin D / Q000378:metabolism / Q000502:physiology*
D018167:Receptors, Calcitriol; D014807:Vitamin D