Role of Vitamin D hydroxylase on Bone Metabolism.

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Vitamin D is a steroid hormone that plays an important role in the maintenance of calcium and mineral metabolism. The 24-hydroxylase (CYP24) enzyme is a cytochrome P450 molecule that is distributed in the target tissues of vitamin D, and is induced specially by 1α, 25 dihydroxyvitamin D_3.Two functions of this enzyme have been revealed so far. One is production of 24, 25 dihydroxyvitamin D_3 from 25-hydroxyvitamin D_3 as a substrate. 24, 25-dihydroxyvitamin D_3 is known to have an effect on bone mass increments when high doses to rats. The other function of CYP24 is to inactivate 1α, 25 dihydroxyvitamin D_3 which strongly induces this enzyme, and to maintain vitamin D homeostasis. In order to clarify the physiological role of CYP24 in vivo, we have over expressed CYP24 in rats. In the present study we examined the mechanism for the alteration in serum vitamin D metabolites levels and analysed the consequent influences on bone metabolism. In CYP24 transgenic rat, we found Out that excessive alubuminures developed from early stages, and as albumin has an ability to bind megalin, a receptor for vitamin D-binding protein. The excretion of 25-hydroxyvitamin D3 in Tg rats increased as albumin excretion increased, and both parameters had a strong positive correlation. Finally we examined the influence of renal dysfunction on bone metabolism. There was a significant decrease in bone mineral density of Tg rats at 8 weeks of age when the serum parathyroid hormone level begins to rise. Infusion of 25-hydroxyvitamin D3 greatly increased the BMD in the tibia of Tg rats. The mechanisms of CYP24 overexpression for induction of nephritis need to be elucidated in future studies.