The vitamin D endocrine system (D-endo) is essential for calcium and bone homeostasis. Absence of a functional VDR or CYP27B1 creates a severe rachitic bone and growth plate phenotype in humans and mice as in severe vitamin D deficiency. The intestine is the key target for VDR as a high calcium intake or selective VDR rescue in the intestine restores a normal bone and growth plate phenotype. Selective absence of VDR in osteoblasts does not create a bone phenotype when calcium intake is normal.
VDR is ubiquitously expressed and about 3% of the mouse or human genome is regulated by D-endo. The native immune defense system is activated by D-endo but VDR or vitamin D deficiency leads to increased sensitivity to autoimmune diseases such as inflammatory bowel disease or autoimmune diabetes after exposure to predisposing factors. VDR deficient mice do not have a spontaneous increase in cancer but are more prone to oncogen, chemocarcinogen or UV-B induced tumors. A wealth of observational studies in men also links a poor vitamin D nutritional status to increased risk of all major cancers. D-endo is also related to the cardiovascular system as VDR or CYP27B1 KO mice develop high renin hypertension, cardiac hypertrophy and increased thrombogenicity. Observational studies in men also link poor vitamin D status to all aspects of the metabolic syndrome and increased risk of cardiovascular diseases. The muscle development of VDR KO mice is delayed and their fertility is impaired.
Whether the same spectrum of activity is also operational in humans is not yet established but vitamin D deficiency is frequently associated with an increased prevalence of diseases expected on the basis of the VDR KO phenotype. Prospective and intervention studies will be presented as to define the spectrum of activities and the optimal vitamin D status for global health.
Declaration of interest: The autjor declares that there is a conflict of interest.
Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.
05 - 09 May 2012
European Society of Endocrinology