Renal and hepatic 1α-hydroxylation of 25-hydroxyvitamin D3 in piglets suffering from pseudo vitamin D-deficiency rickets, type I

AbstractThe piglets examined suffer from rickets and have symptoms similar to those of classic pseudo vitamin D-deficiency rickets, type I (PVDRI), including plasma concentrations of 1α,25-dihydroxyvitamin D3 considerably lower than in healthy control piglets. It has been suggested that the rachitic piglets have a defective renal 1α,25-dihydroxyvitamin D3 production. The present study shows that partially purified mitochondrial and microsomal cytochrome P450 from kidney and liver of both rachitic and control animals is able to catalyze 1α-hydroxylation of 25-hydroxyvitamin D3. The renal mitochondrial 1α-hydroxylase activity was higher in the rachitic piglets whereas the renal microsomal 1α-hydroxylase activity was decreased. The immunodetectable levels in kidney of a mitochondrial 1α-hydroxylase (CYP27) and a microsomal 1α-hydroxylase (vitamin D3 25-hydroxylase) were correlated with the 1α-hydroxylase activities. The results suggest that the renal microsomal 1α-hydroxylase is affected by the rachitic condition. It is concluded that the primary genetic defect of systemic 1α,25-dihydroxyvitamin D3 deficiency in the rachitic PVDRI piglets does not reside in a defective function or absence of renal mitochondrial 25-hydroxyvitamin D3 1α-hydroxylase. From this, it may also be concluded that PVDRI in man and pig appear to be two different forms of the disease