RENAL AND HEPATIC 1-ALPHA-HYDROXYLATION OF 25-HYDROXYVITAMIN D-3 IN PIGLETS SUFFERING FROM PSEUDO VITAMIN-D-DEFICIENCY RICKETS, TYPE-I

The 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 1 alpha,25-dihydroxyvitamin D-3 con siderably lower than in healthy control piglets. It has been suggested that the rachitic piglets have a defective renal 1 alpha,25-dihydroxy vitamin 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 1 alpha-hydroxy lation of 25-hydroxyvitamin D-3. The renal mitochondrial 1 alpha-hydro xylase activity was higher in the rachitic piglets whereas the renal m icrosomal 1 alpha-hydroxylase activity was decreased. The immunodetect able levels in kidney of a mitochondrial 1 alpha-hydroxylase (CYP27) a nd a microsomal 1 alpha-hydroxylase (vitamin D-3 25-hydroxylase) were correlated with the 1 alpha-hydroxylase activities. The results sugges t that the renal microsomal 1 alpha-hydroxylase is affected by the rac hitic condition. It is concluded that the primary genetic defect of sy stemic 1 alpha,25-dihydroxyvitamin D-3 deficiency in the rachitic PVDR I piglets does not reside in a defective function or absence of renal mitochondrial 25-hydroxyvitamin D3 1 alpha-hydroxylase. From this, it may also be concluded that PVDRI in man and pig appear to be two diffe rent forms of the disease. (C) 1998 Elsevier Science B.V. All rights r eserved.