A new mechanism for induced vitamin D deficiency in calcium deprivation.
Synthesis of vitamin D in the skin in response to ultraviolet light is the main determinant of vitamin D status in man and it is therefore surprising that rickets and osteomalacia, clinical signs of vitamin D deficiency, remain common in tropical and subtropical countries. Skin pigmentation can reduce vitamin D formation but this is a negligible limitation in people exposed to abundant ultraviolet light. Earlier studies in animals and man suggested that another environmental factor, the low calcium/high cereal diet typical of susceptible populations, might affect the efficiency of vitamin D utilization. We show here in rats that the rate of inactivation of vitamin D in the liver is increased by calcium deprivation. The effect is mediated by 1,25-dihydroxyvitamin D, produced in response to secondary hyperparathyroidism, which promotes hepatic conversion of vitamin D to polar inactivation products that are excreted in bile. This finding has widespread implications both for understanding the pathogenesis of endemic rickets and in that it provides a unifying mechanism for the development of vitamin D deficiency in many clinical disorders.
D000818:Animals; D001646:Bile / Q000378:metabolism; D002117:Calcitriol / Q000378:metabolism; D002118:Calcium / Q000008:administration & dosage / Q000172:deficiency*; D002762:Cholecalciferol / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005965:Glucuronates / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D010758:Phosphorus / Q000008:administration & dosage; D051381:Rats; D012880:Skin Pigmentation; D013152:Splanchnic Circulation; D014808:Vitamin D Deficiency / Q000209:etiology*
D005965:Glucuronates; D002762:Cholecalciferol; D010758:Phosphorus; D003577:Cytochrome P-450 Enzyme System; D002117:Calcitriol; D002118:Calcium